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Article(id=1211269158726144222, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.04.04, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1587916800000, receivedDateStr=2020-04-27, revisedDate=1613404800000, revisedDateStr=2021-02-16, acceptedDate=null, acceptedDateStr=null, onlineDate=1766718671732, onlineDateStr=2025-12-26, pubDate=1619539200000, pubDateStr=2021-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766718671732, onlineIssueDateStr=2025-12-26, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766718671732, creator=13701087609, updateTime=1766718671732, updator=13701087609, issue=Issue{id=1211269157790806494, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='4', pageStart='319', pageEnd='424', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766718671510, creator=13701087609, updateTime=1766718756000, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269512217882745, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269512217882746, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1211269157790806494, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=340, endPage=347, ext={EN=ArticleExt(id=1211269159011356895, articleId=1211269158726144222, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Correlation analysis between Toll-like receptor genomic characteristics and clinicopathological and immune parameters in rectal cancer, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the effects of Toll-like receptors (TLR3/TLR4/TLR5/TLR7) on the development, prognosis and immune characteristics of rectal cancer and to explore the association of genetic variation in the regulation region of TLRs with the risk for rectal cancer. Methods Gene expression profiling interactive analysis (GEPIA) platform was used to analyze the expression of TLRs in rectal cancer and its relationship with prognosis. Transcriptome data and clinical data of rectal cancer were downloaded from TCGA database and the correlation between TLRs expression and pathological stage was analyzed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of TLR4 rs1927914 and rs7869402 polymorphism. TaqMan probe method was used to determine the genotypes of TLR3 rs5743303, TLR5 rs1640816 and TLR7 rs7869402 variants. The association of TLRs genetic variants with the rectal cancer risk was analyzed by unconditional logistic regression. The immune cells in rectal cancer samples were scored using ESTIMATE algorithm. Using TIMER online data platform, the relationship between both the expression of TLRs and copy number variation (CNV) of genes and immune infiltrated cells was evaluated. Gene function related to TLR3 expression was evaluated by GO function enrichment analysis, gene set variation analysis(GSVA) was used to predict the regulatory network of TLR3 in rectal cancer. Results TLR3 has a lower expression in rectal cancer tissues than in adjacent tissues, which was related to poor prognosis. Compared with the individuals carrying TLR3 AA genotype, the individuals with at least one TLR3 rs5743303 T allele had significantly higher risk of rectal cancer (OR=1.43, 95%CI 1.07-1.91).The study did not show that TLR4 rs1927914, TLR4 rs7869402, TLR5 rs1640816 and TLR7 rs3853839 polymorphism had effect on the risk for rectal cancer. After stratified analysis, the data showed that TLR3 rs5743303 AT or TT contributed the susceptibility to rectal cancer in males (OR=1.47, 95%CI 1.01-2.11), younger subjects (OR=1.64, 95%CI 1.08-2.47), smokers (OR=2.42, 95%CI 1.37-4.38) and drinkers (OR=2.70, 95%CI 1.52-4.80). ESTIMATE and TIMER analyses showed that TLR3 effected on the immune cell infiltration. The results of GO functional enrichment analysis showed that TLR3 was mainly related to changes in related functions such as receptor ligand activity, antigen binding, immunoglobulin receptor binding, growth factors and cytokines. GSVA results showed that TLR3 inhibited the development of rectal cancer by regulating metabolic or immune-related pathways, such as cell apoptosis, natural killer cell-mediated cytotoxicity, phospholipid metabolism and autophagy regulation. Conclusion TLR3 effects on the occurrence and prognosis of rectal cancer and rs5743303 polymorphism increase the susceptibility to rectal cancer.

, correspAuthors=Xue-Mei Zhang, authorNote=null, correspAuthorsNote=
*E-mail:
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目的 探讨Toll样受体家族成员对直肠癌发生、预后和免疫特征的影响，以及其基因调节区遗传变异与直肠癌发病风险的关系。方法 使用GEPIA平台分析Toll样受体3(TLR3)、TLR4、TLR5和TLR7在直肠癌中的表达及其与预后的关系。从TCGA数据库获取直肠癌mRNA转录组数据和临床资料，分析TLR3表达与病理分期的关系。使用PCR-RFLP技术对TLR4 rs1927914、rs7869402多态进行基因分型，使用TaqMan探针法对TLR3 rs5743303、TLR5 rs1640816、TLR7 rs7869402多态进行基因分型。应用非条件logistic回归分析TLRs遗传变异与直肠癌发病风险的关系。使用ESTIMATE对直肠癌样本的免疫细胞进行评分，通过TIMER在线数据平台分析TLR3表达及拷贝数变异(CNV)与免疫细胞浸润的关系。GO功能富集分析TLR3相关差异基因的表达，基因集变异分析(GSVA)预测直肠癌中TLR3的调控网络。结果 TLR3在直肠癌组织中呈低表达，且其低表达与预后不良有关。与TLR3 rs5743303 AA基因型相比，AT或TT基因型携带者的直肠癌发病风险明显升高(OR=1.43，95%CI 1.07~1.91)。TLR4 rs1927914、TLR4 rs7869402、TLR5 rs1640816及TLR7 rs3853839多态不影响直肠癌的发病风险。分层分析结果显示，TLR3 rs5743303 AT或TT基因型可增加男性(OR=1.47，95%CI 1.01~2.11)、低年龄者(OR=1.64，95%CI 1.08~2.47)、吸烟者(OR=2.42，95%CI 1.37~4.38)和饮酒者(OR=2.70，95%CI 1.52~4.80)直肠癌的发病风险。ESTIMATE和TIMER分析结果显示，TLR3与免疫细胞浸润具有一定相关性。GO功能富集分析结果显示，TLR3主要与受体配体活性、抗原结合、免疫球蛋白受体结合、生长因子和细胞因子等相关功能的改变有关。GSVA分析结果显示，TLR3可通过调节细胞凋亡、自然杀伤细胞介导的细胞毒性、磷脂代谢及自噬调节等与代谢或免疫相关的途径而抑制直肠癌的发生发展。结论 TLR3与直肠癌的发生及预后相关，TLR3 rs5743303遗传变异可影响直肠癌的遗传易感性。

, correspAuthors=张雪梅, authorNote=null, correspAuthorsNote=
张雪梅，E-mail：
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李昂，硕士研究生，主要从事分子肿瘤学方面的研究

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李昂，硕士研究生，主要从事分子肿瘤学方面的研究

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李昂，硕士研究生，主要从事分子肿瘤学方面的研究

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tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, orderNo=4, keyword=直肠癌)], refs=[Reference(id=1211269167395770932, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2020, volume=70, issue=3, pageStart=145, pageEnd=164, url=null, language=null, rfNumber=[1], rfOrder=0, authorNames=Siegel RL, Miller KD, Goding Sauer A, journalName=CA Cancer J Clin, refType=null, unstructuredReference=Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164., articleTitle=Colorectal cancer statistics, 2020, refAbstract=null), Reference(id=1211269167483851321, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=144, issue=5, pageStart=646, pageEnd=674, url=null, language=null, rfNumber=[2], rfOrder=1, authorNames=Hanahan D, Weinberg RA, journalName=Cell, refType=null, unstructuredReference=Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144(5): 646-674., articleTitle=Hallmarks of cancer: The next generation, refAbstract=null), Reference(id=1211269167567737407, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=44, issue=8, pageStart=648, pageEnd=651, url=null, language=null, rfNumber=[3], rfOrder=2, authorNames=Bao LL, Cui LH, journalName=Med J Chin PLA, refType=null, unstructuredReference=Bao LL, Cui LH. Exprossion of TLR4 and NF-κB in rats model induced with IBS-D and its mechanism[J]. Med J Chin PLA, 2019, 44(8): 648-651., articleTitle=Exprossion of TLR4 and NF-κB in rats model induced with IBS-D and its mechanism, refAbstract=null), Reference(id=1211269167660012099, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=44, issue=8, pageStart=648, pageEnd=651, url=null, language=null, rfNumber=[3], rfOrder=3, authorNames=鲍璐璐, 崔立红, journalName=解放军医学杂志, refType=null, unstructuredReference=[鲍璐璐, 崔立红. IBS-D大鼠结肠TLR4、NF-κB的表达变化及机制[J]. 解放军医学杂志, 2019, 44(8): 648-651.], articleTitle=IBS-D大鼠结肠TLR4、NF-κB的表达变化及机制, refAbstract=null), Reference(id=1211269167752286790, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2000, volume=343, issue=2, pageStart=78, pageEnd=85, url=null, language=null, rfNumber=[4], rfOrder=4, authorNames=Lichtenstein P, Holm NV, Verkasalo PK, journalName=N Engl J Med, refType=null, unstructuredReference=Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland[J]. N Engl J Med, 2000, 343(2): 78-85., articleTitle=Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland, refAbstract=null), Reference(id=1211269167873921612, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2010, volume=138, issue=6, pageStart=2044, pageEnd=2058, url=null, language=null, rfNumber=[5], rfOrder=5, authorNames=Kory WJ, Thérèse MT, Deborah WN, journalName=Gastroenterology, refType=null, unstructuredReference=Kory WJ, Thérèse MT, Deborah WN, et al. Hereditary and familial colon cancer[J]. Gastroenterology, 2010, 138(6): 2044-2058., articleTitle=Hereditary and familial colon cancer, refAbstract=null), Reference(id=1211269167962001999, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2014, volume=15, issue=4, pageStart=199, pageEnd=209, url=null, language=null, rfNumber=[6], rfOrder=6, authorNames=Trejo-de la OA, Hernández-Sancén P, Maldonado-Bernal C, journalName=Genes Immun, refType=null, unstructuredReference=Trejo-de la OA, Hernández-Sancén P, Maldonado-Bernal C.Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer[J]. Genes Immun, 2014, 15(4): 199-209., articleTitle=Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer, refAbstract=null), Reference(id=1211269168062665301, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2017, volume=162, issue=6, pageStart=1717, pageEnd=1723, url=null, language=null, rfNumber=[7], rfOrder=7, authorNames=He H, Liu S, Liu PP, journalName=Arch Virol, refType=null, unstructuredReference=He H, Liu S, Liu PP, et al. Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children[J]. Arch Virol, 2017, 162(6): 1717-1723., articleTitle=Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children, refAbstract=null), Reference(id=1211269168150745689, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2020, volume=30, issue=6, pageStart=464, pageEnd=470, url=null, language=null, rfNumber=[8], rfOrder=8, authorNames=He YT, Liu L, journalName=New Medicine, refType=null, unstructuredReference=He YT, Liu L. Relationship between the gut microbiome and the development of colorectal cancer[J]. New Medicine, 2020, 30(6): 464-470., articleTitle=Relationship between the gut microbiome and the development of colorectal cancer, refAbstract=null), Reference(id=1211269168268186205, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2020, volume=30, issue=6, pageStart=464, pageEnd=470, url=null, language=null, rfNumber=[8], rfOrder=9, authorNames=何杨婷, 刘莉, journalName=医学新知, refType=null, unstructuredReference=[何杨婷, 刘莉. 肠道菌群与结直肠癌发生发展的关系[J]. 医学新知, 2020, 30(6): 464-470.], articleTitle=肠道菌群与结直肠癌发生发展的关系, refAbstract=null), Reference(id=1211269168364655201, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=35, issue=11, pageStart=1572, pageEnd=1574, url=null, language=null, rfNumber=[9], rfOrder=10, authorNames=Gong J, Yuan GP, Lin YJ, journalName=Chin J Publ Heal, refType=null, unstructuredReference=Gong J, Yuan GP, Lin YJ, et al. Outcomes of high risk assessment and clinical screening on cancer among community residents in Jiangbei district of Ningbo city: 2013-2017[J]. Chin J Publ Heal, 2019, 35(11): 1572-1574., articleTitle=Outcomes of high risk assessment and clinical screening on cancer among community residents in Jiangbei district of Ningbo city: 2013-2017, refAbstract=null), Reference(id=1211269168473707109, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=35, issue=11, pageStart=1572, pageEnd=1574, url=null, language=null, rfNumber=[9], rfOrder=11, authorNames=龚静, 元国平, 林寅君, journalName=中国公共卫生, refType=null, unstructuredReference=[龚静, 元国平, 林寅君, 等. 宁波市江北区2013－2017年度居民癌症高风险评估及临床筛查结果分析[J]. 中国公共卫生, 2019, 35(11): 1572-1574.], articleTitle=宁波市江北区2013－2017年度居民癌症高风险评估及临床筛查结果分析, refAbstract=null), Reference(id=1211269168586953320, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=95, issue=3, pageStart=e2582, pageEnd=null, url=null, language=null, rfNumber=[10], rfOrder=12, authorNames=Huh JW, Kim HC, Kim SH, journalName=Medicine (Baltimore), refType=null, unstructuredReference=Huh JW, Kim HC, Kim SH, et al. Mismatch repair gene expression as a predictor of tumor responses in patients with rectal cancer treated with preoperative chemoradiation[J]. Medicine (Baltimore), 2016, 95(3): e2582., articleTitle=Mismatch repair gene expression as a predictor of tumor responses in patients with rectal cancer treated with preoperative chemoradiation, refAbstract=null), Reference(id=1211269168708588139, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2018, volume=59, issue=null, pageStart=391, pageEnd=412, url=null, language=null, rfNumber=[11], rfOrder=13, authorNames=Vijay K, journalName=Int Immunopharmacol, refType=null, unstructuredReference=Vijay K. Toll-like receptors in immunity and inflammatory diseases: Past, present, and future[J]. Int Immunopharmacol, 2018, 59: 391-412., articleTitle=Toll-like receptors in immunity and inflammatory diseases: Past, present, and future, refAbstract=null), Reference(id=1211269168968634995, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2020, volume=146, issue=5, pageStart=1409, pageEnd=1420, url=null, language=null, rfNumber=[12], rfOrder=14, authorNames=Bellmann L, Cappellano G, Schachtl-Riess JF, journalName=Int J Cancer, refType=null, unstructuredReference=Bellmann L, Cappellano G, Schachtl-Riess JF, et al. A TLR7 agonist strengthens T and NK cell function during BRAF-targeted therapy in a preclinical melanoma model[J]. Int J Cancer, 2020, 146(5): 1409-1420., articleTitle=A TLR7 agonist strengthens T and NK cell function during BRAF-targeted therapy in a preclinical melanoma model, refAbstract=null), Reference(id=1211269169169961591, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2020, volume=1223, issue=null, pageStart=81, pageEnd=97, url=null, language=null, rfNumber=[13], rfOrder=15, authorNames=McCall KD, Muccioli M, Benencia F, journalName=Adv Exp Med Biol, refType=null, unstructuredReference=McCall KD, Muccioli M, Benencia F. Toll-like receptors signaling in the tumor microenvironment[J]. Adv Exp Med Biol, 2020, 1223: 81-97., articleTitle=Toll-like receptors signaling in the tumor microenvironment, refAbstract=null), Reference(id=1211269169316762235, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2009, volume=183, issue=6, pageStart=3634, pageEnd=3641, url=null, language=null, rfNumber=[14], rfOrder=16, authorNames=Pulko V, Liu X, Krco CJ, journalName=J Immunol, refType=null, unstructuredReference=Pulko V, Liu X, Krco CJ, et al. TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination[J]. J Immunol, 2009, 183(6): 3634-3641., articleTitle=TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination, refAbstract=null), Reference(id=1211269169446785664, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=71, issue=4, pageStart=763, pageEnd=772, url=null, language=null, rfNumber=[15], rfOrder=17, authorNames=Bonnin M, Fares N, Testoni B, journalName=J Hepatol, refType=null, unstructuredReference=Bonnin M, Fares N, Testoni B, et al. Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis[J]. J Hepatol, 2019, 71(4): 763-772., articleTitle=Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis, refAbstract=null), Reference(id=1211269169555837573, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2017, volume=18, issue=10, pageStart=747, pageEnd=756, url=null, language=null, rfNumber=[16], rfOrder=18, authorNames=Bianchi F, Pretto S, Tagliabue E, journalName=Cancer Biol Ther, refType=null, unstructuredReference=Bianchi F, Pretto S, Tagliabue E, et al. Exploiting poly(I: C) to induce cancer cell apoptosis[J]. Cancer Biol Ther, 2017, 18(10): 747-756., articleTitle=Exploiting poly(I: C) to induce cancer cell apoptosis, refAbstract=null), Reference(id=1211269169656500873, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2018, volume=216, issue=2, pageStart=319, pageEnd=325, url=null, language=null, rfNumber=[17], rfOrder=19, authorNames=Sato Y, Motoyama S, Wakita A, journalName=Am J Surg, refType=null, unstructuredReference=Sato Y, Motoyama S, Wakita A, et al. TLR3 expression status predicts prognosis in patients with advanced thoracic esophageal squamous cell carcinoma after esophagectomy[J]. Am J Surg, 2018, 216(2): 319-325., articleTitle=TLR3 expression status predicts prognosis in patients with advanced thoracic esophageal squamous cell carcinoma after esophagectomy, refAbstract=null), Reference(id=1211269169752969874, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=9, issue=1, pageStart=14288, pageEnd=null, url=null, language=null, rfNumber=[18], rfOrder=20, authorNames=Bianchi F, Milione M, Casalini P, journalName=Sci Rep, refType=null, unstructuredReference=Bianchi F, Milione M, Casalini P, et al. Toll-like receptor 3 as a new marker to detect high risk early stage non-small-cell lung cancer patients[J]. Sci Rep, 2019, 9(1): 14288., articleTitle=Toll-like receptor 3 as a new marker to detect high risk early stage non-small-cell lung cancer patients, refAbstract=null), Reference(id=1211269169882993300, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2015, volume=4, issue=10, pageStart=e1040214, pageEnd=null, url=null, language=null, rfNumber=[19], rfOrder=21, authorNames=Le Noci V, Tortoreto M, Gulino A, journalName=Oncoimmunology, refType=null, unstructuredReference=Le Noci V, Tortoreto M, Gulino A, et al. Poly(I: C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment[J]. Oncoimmunology, 2015, 4(10): e1040214., articleTitle=Poly(I: C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment, refAbstract=null), Reference(id=1211269169979462298, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=5, issue=11, pageStart=e1234571, pageEnd=null, url=null, language=null, rfNumber=[20], rfOrder=22, authorNames=Le Noci V, Sommariva M, Tortoreto M, journalName=Oncoimmunology, refType=null, unstructuredReference=Le Noci V, Sommariva M, Tortoreto M, et al. Reprogramming the lung microenvironment by inhaled immunotherapy fosters immune destruction of tumor[J]. Oncoimmunology, 2016, 5(11): e1234571., articleTitle=Reprogramming the lung microenvironment by inhaled immunotherapy fosters immune destruction of tumor, refAbstract=null), Reference(id=1211269170763797155, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2012, volume=109, issue=6, pageStart=2066, pageEnd=2071, url=null, language=null, rfNumber=[21], rfOrder=23, authorNames=Shime H, Matsumoto M, Oshiumi H, journalName=Proc Natl Acad Sci U S A, refType=null, unstructuredReference=Shime H, Matsumoto M, Oshiumi H, et al. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors[J]. Proc Natl Acad Sci U S A, 2012, 109(6): 2066-2071., articleTitle=Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors, refAbstract=null), Reference(id=1211269170877043367, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=4, issue=7, pageStart=563, pageEnd=568, url=null, language=null, rfNumber=[22], rfOrder=24, authorNames=Sweis RF, Spranger S, Bao R, journalName=Cancer Immunol Res, refType=null, unstructuredReference=Sweis RF, Spranger S, Bao R, et al. Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer[J]. Cancer Immunol Res, 2016, 4(7): 563-568., articleTitle=Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer, refAbstract=null), Reference(id=1211269170981900970, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2012, volume=103, issue=4, pageStart=653, pageEnd=658, url=null, language=null, rfNumber=[23], rfOrder=25, authorNames=Yang ZH, Dai Q, Gu YJ, journalName=Cancer Sci, refType=null, unstructuredReference=Yang ZH, Dai Q, Gu YJ, et al. Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma[J]. Cancer Sci, 2012, 103(4): 653-658., articleTitle=Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma, refAbstract=null), Reference(id=1211269171057398447, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2012, volume=4, issue=null, pageStart=23, pageEnd=29, url=null, language=null, rfNumber=[24], rfOrder=26, authorNames=Kutikhin AG, Yuzhalin AE, journalName=Cancer Manag Res, refType=null, unstructuredReference=Kutikhin AG, Yuzhalin AE. Are Toll-like receptor gene polymorphisms associated with prostate cancer?[J]. Cancer Manag Res, 2012, 4: 23-29., articleTitle=Are Toll-like receptor gene polymorphisms associated with prostate cancer?, refAbstract=null), Reference(id=1211269171145478836, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=12, issue=6, pageStart=344, pageEnd=357, url=null, language=null, rfNumber=[25], rfOrder=27, authorNames=Joosten LA, Abdollahi-Roodsaz S, Dinarello CA, journalName=Nat Rev Rheumatol, refType=null, unstructuredReference=Joosten LA, Abdollahi-Roodsaz S, Dinarello CA, et al. Toll-like receptors and chronic inflammation in rheumatic diseases: new developments[J]. Nat Rev Rheumatol, 2016, 12(6): 344-357., articleTitle=Toll-like receptors and chronic inflammation in rheumatic diseases: new developments, refAbstract=null), Reference(id=1211269171229364918, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2012, volume=13, issue=6, pageStart=535, pageEnd=542, url=null, language=null, rfNumber=[26], rfOrder=28, authorNames=Netea MG, Wijmenga C, O'Neill LAG, journalName=Nat Immunol, refType=null, unstructuredReference=Netea MG, Wijmenga C, O'Neill LAG. Genetic variation in Toll-like receptors and disease susceptibility[J]. Nat Immunol, 2012, 13(6): 535-542., articleTitle=Genetic variation in Toll-like receptors and disease susceptibility, refAbstract=null), Reference(id=1211269171359388348, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2014, volume=20, issue=4, pageStart=416, pageEnd=424, url=null, language=null, rfNumber=[27], rfOrder=29, authorNames=Zeljic K, Supic G, Jovic N, journalName=Oral Dis, refType=null, unstructuredReference=Zeljic K, Supic G, Jovic N, et al. Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival[J]. Oral Dis, 2014, 20(4): 416-424., articleTitle=Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival, refAbstract=null), Reference(id=1211269171506188994, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2019, volume=8, issue=6, pageStart=e1593801, pageEnd=null, url=null, language=null, rfNumber=[28], rfOrder=30, authorNames=Fan L, Zhou P, Hong Q, journalName=Oncoimmunology, refType=null, unstructuredReference=Fan L, Zhou P, Hong Q, et al. Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: A two-stage association study and functional investigation[J]. Oncoimmunology, 2019, 8(6): e1593801., articleTitle=Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: A two-stage association study and functional investigation, refAbstract=null), Reference(id=1211269171598463686, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=72, issue=2, pageStart=193, pageEnd=206, url=null, language=null, rfNumber=[29], rfOrder=31, authorNames=Kutikhin AG, journalName=Hum Immunol, refType=null, unstructuredReference=Kutikhin AG. Impact of Toll-like receptor 4 polymorphisms on risk of cancer[J]. Hum Immunol, 2011, 72(2): 193-206., articleTitle=Impact of Toll-like receptor 4 polymorphisms on risk of cancer, refAbstract=null), Reference(id=1211269171682349771, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=71, issue=2, pageStart=123, pageEnd=129, url=null, language=null, rfNumber=[30], rfOrder=32, authorNames=Hart K, Landvik NE, Lind H, journalName=Lung Cancer, refType=null, unstructuredReference=Hart K, Landvik NE, Lind H, et al. A combination of functional polymorphisms in the CASP8, MMP1, IL10 and SEPS1 genes affects risk of non-small cell lung cancer[J]. Lung Cancer, 2011, 71(2): 123-129., articleTitle=A combination of functional polymorphisms in the CASP8, MMP1, IL10 and SEPS1 genes affects risk of non-small cell lung cancer, refAbstract=null), Reference(id=1211269171774624465, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2009, volume=190, issue=2, pageStart=88, pageEnd=92, url=null, language=null, rfNumber=[31], rfOrder=33, authorNames=Song J, Kim DY, Kim CS, journalName=Cancer Genet Cytogenet, refType=null, unstructuredReference=Song J, Kim DY, Kim CS, et al. The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of prostate cancer in Korean men[J]. Cancer Genet Cytogenet, 2009, 190(2): 88-92., articleTitle=The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of prostate cancer in Korean men, refAbstract=null), Reference(id=1211269171879482067, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=6, issue=4, pageStart=e19466, pageEnd=null, url=null, language=null, rfNumber=[32], rfOrder=34, authorNames=Shi M, Xu X, Chen H, journalName=PLoS One, refType=null, unstructuredReference=Shi M, Xu X, Chen H, et al. Single nucleotide polymorphisms of Toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma[J]. PLoS One, 2011, 6(4): e19466., articleTitle=Single nucleotide polymorphisms of Toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma, refAbstract=null), Reference(id=1211269172013699800, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2010, volume=24, issue=2, pageStart=100, pageEnd=106, url=null, language=null, rfNumber=[33], rfOrder=35, authorNames=Huang H, Wu J, Jin G, journalName=J Biomed Res, refType=null, unstructuredReference=Huang H, Wu J, Jin G, et al. A 5'-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population[J]. J Biomed Res, 2010, 24(2): 100-106., articleTitle=A 5'-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population, refAbstract=null), Reference(id=1211269172173083361, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=17, issue=3, pageStart=677, pageEnd=683, url=null, language=null, rfNumber=[34], rfOrder=36, authorNames=Pimentel-Nunes P, Afonso L, Lopes P, journalName=Pathol Oncol Res, refType=null, unstructuredReference=Pimentel-Nunes P, Afonso L, Lopes P, et al. Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia[J]. Pathol Oncol Res, 2011, 17(3): 677-683., articleTitle=Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia, refAbstract=null), Reference(id=1211269172277940963, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2013, volume=108, issue=3, pageStart=638, pageEnd=643, url=null, language=null, rfNumber=[35], rfOrder=37, authorNames=Kauppila JH, Mattila AE, Karttunen TJ, journalName=Br J Cancer, refType=null, unstructuredReference=Kauppila JH, Mattila AE, Karttunen TJ, et al. Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue[J]. Br J Cancer, 2013, 108(3): 638-643., articleTitle=Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue, refAbstract=null), Reference(id=1211269172374409961, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2011, volume=60, issue=9, pageStart=1211, pageEnd=1220, url=null, language=null, rfNumber=[36], rfOrder=38, authorNames=Pinto A, Morello S, Sorrentino R, journalName=Cancer Immunol Immunother, refType=null, unstructuredReference=Pinto A, Morello S, Sorrentino R. Lung cancer and Toll-like receptors[J]. Cancer Immunol Immunother, 2011, 60(9): 1211-1220., articleTitle=Lung cancer and Toll-like receptors, refAbstract=null), Reference(id=1211269172491850477, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2017, volume=8, issue=51, pageStart=88622, pageEnd=88629, url=null, language=null, rfNumber=[37], rfOrder=39, authorNames=Chen S, Yuan W, Fu Z, journalName=Oncotarget, refType=null, unstructuredReference=Chen S, Yuan W, Fu Z, et al. Toll-like receptor 5 gene polymorphism is associated with breast cancer susceptibility[J]. Oncotarget, 2017, 8(51): 88622-88629., articleTitle=Toll-like receptor 5 gene polymorphism is associated with breast cancer susceptibility, refAbstract=null), Reference(id=1211269172638651120, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2009, volume=44, issue=8, pageStart=803, pageEnd=811, url=null, language=null, rfNumber=[38], rfOrder=40, authorNames=Uematsu S, Akira S, journalName=J Gastroenterol, refType=null, unstructuredReference=Uematsu S, Akira S. Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection[J]. J Gastroenterol, 2009, 44(8): 803-811., articleTitle=Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection, refAbstract=null), Reference(id=1211269172735120114, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=44, issue=4, pageStart=889, pageEnd=900, url=null, language=null, rfNumber=[39], rfOrder=41, authorNames=Yang JY, Kim MS, Kim E, journalName=Immunity, refType=null, unstructuredReference=Yang JY, Kim MS, Kim E, et al. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production[J]. Immunity, 2016, 44(4): 889-900., articleTitle=Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production, refAbstract=null), Reference(id=1211269172827394805, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2016, volume=7, issue=37, pageStart=59017, pageEnd=59028, url=null, language=null, rfNumber=[40], rfOrder=42, authorNames=Gao X, Zhang Y, Breitling LP, journalName=Oncotarget, refType=null, unstructuredReference=Gao X, Zhang Y, Breitling LP, et al. Tobacco smoking and methylation of genes related to lung cancer development[J]. Oncotarget, 2016, 7(37): 59017-59028., articleTitle=Tobacco smoking and methylation of genes related to lung cancer development, refAbstract=null), Reference(id=1211269172965806841, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2015, volume=7, issue=null, pageStart=113, pageEnd=null, url=null, language=null, rfNumber=[41], rfOrder=43, authorNames=Gao X, Jia M, Zhang Y, journalName=Clin Epigenetics, refType=null, unstructuredReference=Gao X, Jia M, Zhang Y, et al. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: A systematic review of DNA methylation studies[J]. Clin Epigenetics, 2015, 7: 113., articleTitle=DNA methylation changes of whole blood cells in response to active smoking exposure in adults: A systematic review of DNA methylation studies, refAbstract=null), Reference(id=1211269173062275836, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2015, volume=24, issue=1, pageStart=6, pageEnd=15, url=null, language=null, rfNumber=[42], rfOrder=44, authorNames=Cheng J, Chen Y, Wang X, journalName=Eur J Cancer Prev, refType=null, unstructuredReference=Cheng J, Chen Y, Wang X, et al. Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers[J]. Eur J Cancer Prev, 2015, 24(1): 6-15., articleTitle=Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers, refAbstract=null), Reference(id=1211269173154550526, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, doi=null, pmid=null, pmcid=null, year=2017, volume=31, issue=5, pageStart=561, pageEnd=568, url=null, language=null, rfNumber=[43], rfOrder=45, authorNames=Fagunwa IO, Loughrey MB, Coleman HG, journalName=Best Pract Res Clin Gastroenterol, refType=null, unstructuredReference=Fagunwa IO, Loughrey MB, Coleman HG. Alcohol, smoking and the risk of premalignant and malignant colorectal neoplasms[J]. 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A. TLR3；B. TLR4；C. TLR5；D. TLR7；与正常组织比较，(1)P<0.05。

, figureFileSmall=2vPE4mbwwEPUU5REzEJPHQ==, figureFileBig=Lnvv86Dmv+6fbn07HZZr8A==, tableContent=null), ArticleFig(id=1211269164749165010, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=EN, label=Fig.2, caption=Correlation analysis between TLR3 and immune characteristic parameters, figureFileSmall=HQqUekmdNK5Hb7+/Qhng3w==, figureFileBig=ooKyEn5ikIgte+yQaUzLyg==, tableContent=null), ArticleFig(id=1211269164854022619, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, label=图2, caption=TLR3与免疫特性参数的相关性分析

A. TLR3表达与免疫评分的相关性分析；B. 体细胞TLR3拷贝数变异与免疫浸润的相关性分析；C. TLR3表达与免疫浸润的相关性分析

, figureFileSmall=HQqUekmdNK5Hb7+/Qhng3w==, figureFileBig=ooKyEn5ikIgte+yQaUzLyg==, tableContent=null), ArticleFig(id=1211269164942103010, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=EN, label=Fig.3, caption=Effect of TLR3 expression on gene function and signal pathway, figureFileSmall=2q68pwaCk+2X0ttuNBZTWA==, figureFileBig=UWjKVLMwu4Lv+s5LMHKqnA==, tableContent=null), ArticleFig(id=1211269165034377710, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, label=图3, caption=TLR3表达对基因功能和信号通路的影响

A. GO功能分析；B. GSVA富集分析

, figureFileSmall=2q68pwaCk+2X0ttuNBZTWA==, figureFileBig=UWjKVLMwu4Lv+s5LMHKqnA==, tableContent=null), ArticleFig(id=1211269165101486581, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=EN, label=Tab.1, caption=

Comparison of basic data between patients and controls[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目病例组(n=480)对照组(n=480)χ2P
性别  0.0040.947
 男301(62.7)302(62.9)
 女179(37.3)178(37.1)
年龄(岁)  0.0670.796
 ≤60246(51.3)250(52.1)
 >60234(48.8)230(47.9)
吸烟  0.3340.563
 是128(26.7)136(28.3)
 否352(73.3)344(71.7)
饮酒  0.2340.629
 是158(32.9)151(31.5)
 否322(67.1)329(68.5)
累计吸烟量(包年)*  0.7630.382
 <3059(12.3)70(14.6)
 ≥3069(14.4)66(13.8)  
), ArticleFig(id=1211269165206344185, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, label=表1, caption=

病例组与对照组基本资料比较[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
项目病例组(n=480)对照组(n=480)χ2P
性别  0.0040.947
 男301(62.7)302(62.9)
 女179(37.3)178(37.1)
年龄(岁)  0.0670.796
 ≤60246(51.3)250(52.1)
 >60234(48.8)230(47.9)
吸烟  0.3340.563
 是128(26.7)136(28.3)
 否352(73.3)344(71.7)
饮酒  0.2340.629
 是158(32.9)151(31.5)
 否322(67.1)329(68.5)
累计吸烟量(包年)*  0.7630.382
 <3059(12.3)70(14.6)
 ≥3069(14.4)66(13.8)  
), ArticleFig(id=1211269165420253697, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=EN, label=Tab.2, caption=

Relations of TLR genetic variation to the susceptibility of rectal cancer [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
基因型病例组(n=480)对照组(n=480)OR(95% CI)aP
TLR3 rs5743303
 AA335(69.8)368(76.7)
 AT128(26.7)100(20.8)1.41(1.04~1.91)0.025
 TT17(3.5)12(2.5)1.57(0.74~3.33)0.243
 AT+TT145(30.2)112(23.3)1.43(1.07~1.91)0.015
TLR4 rs7869402
 CC434(90.4)414(86.3)
 CT43(9.0)62(12.9)0.66(0.44~0.99)0.049
 TT3(0.6)4(0.8)0.73(0.16~3.32)0.688
 CT+TT46(9.6)66(13.8)0.66(0.45~0.99)0.050
TLR4 rs1927914
 AA178(37.1)150(31.3)
 AG220(45.8)250(52.1)0.74(0.56~0.98)0.038
 GG82(17.1)80(16.7)0.86(0.59~1.26)0.441
 AG+GG302(62.9)330(68.8)0.77(0.59~1.01)0.057
TLR5 rs1640816
 GG374(77.9)395(82.3)
 AG103(21.5)82(17.1)1.33(0.97~1.84)0.080
 AA3(0.6)3(0.6)1.02(0.20~5.10)0.980
 AG+AA106(22.1)83(17.3)1.32(0.96~1.82)0.085
TLR7 rs3853839
 男
  GG105(21.9)112(23.3)
  GC63(13.1)61(12.7)0.96(0.61~1.52)0.879
  CC11(2.3)5(1.0)1.89(0.61~5.89)0.270
  GC+CC74(15.4)66(13.8)1.03(0.67~1.60)0.886
 女
  G238(49.6)225(46.9)
  C63(13.1)77(16.0)0.79(0.54~1.15)0.217
), ArticleFig(id=1211269165491556870, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, label=表2, caption=

Toll样受体遗传变异与直肠癌易感性的关系[例(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
基因型病例组(n=480)对照组(n=480)OR(95% CI)aP
TLR3 rs5743303
 AA335(69.8)368(76.7)
 AT128(26.7)100(20.8)1.41(1.04~1.91)0.025
 TT17(3.5)12(2.5)1.57(0.74~3.33)0.243
 AT+TT145(30.2)112(23.3)1.43(1.07~1.91)0.015
TLR4 rs7869402
 CC434(90.4)414(86.3)
 CT43(9.0)62(12.9)0.66(0.44~0.99)0.049
 TT3(0.6)4(0.8)0.73(0.16~3.32)0.688
 CT+TT46(9.6)66(13.8)0.66(0.45~0.99)0.050
TLR4 rs1927914
 AA178(37.1)150(31.3)
 AG220(45.8)250(52.1)0.74(0.56~0.98)0.038
 GG82(17.1)80(16.7)0.86(0.59~1.26)0.441
 AG+GG302(62.9)330(68.8)0.77(0.59~1.01)0.057
TLR5 rs1640816
 GG374(77.9)395(82.3)
 AG103(21.5)82(17.1)1.33(0.97~1.84)0.080
 AA3(0.6)3(0.6)1.02(0.20~5.10)0.980
 AG+AA106(22.1)83(17.3)1.32(0.96~1.82)0.085
TLR7 rs3853839
 男
  GG105(21.9)112(23.3)
  GC63(13.1)61(12.7)0.96(0.61~1.52)0.879
  CC11(2.3)5(1.0)1.89(0.61~5.89)0.270
  GC+CC74(15.4)66(13.8)1.03(0.67~1.60)0.886
 女
  G238(49.6)225(46.9)
  C63(13.1)77(16.0)0.79(0.54~1.15)0.217
), ArticleFig(id=1211269165567054344, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=EN, label=Tab.3, caption=

Stratified analysis of TLR3 rs5743303 genotypes with the risk of rectal cancer

, figureFileSmall=null, figureFileBig=null, tableContent=
项目基因型(病例/对照)(AT+TT)/AA OR(95%CI)aP
AAAT+TT
性别
 男210/23391/691.47(1.01~2.11)0.041
 女125/13554/431.37(0.84~2.21)0.202
年龄(岁)
 ≤60172/19774/531.64(1.08~2.47)0.019
 >60163/17171/591.32(0.87~2.00)0.185
吸烟
 是82/10948/272.42(1.37~4.38)0.002
 否253/25997/851.19(0.85~1.67)0.315
饮酒
 是106/12553/262.70(1.52~4.80)0.001
 否229/24393/861.16(0.82~1.64)0.395
), ArticleFig(id=1211269166766625294, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1211269158726144222, language=CN, label=表3, caption=

TLR3 rs5743303基因分型与直肠癌发病风险的分层分析

, figureFileSmall=null, figureFileBig=null, tableContent=
项目基因型(病例/对照)(AT+TT)/AA OR(95%CI)aP
AAAT+TT
性别
 男210/23391/691.47(1.01~2.11)0.041
 女125/13554/431.37(0.84~2.21)0.202
年龄(岁)
 ≤60172/19774/531.64(1.08~2.47)0.019
 >60163/17171/591.32(0.87~2.00)0.185
吸烟
 是82/10948/272.42(1.37~4.38)0.002
 否253/25997/851.19(0.85~1.67)0.315
饮酒
 是106/12553/262.70(1.52~4.80)0.001
 否229/24393/861.16(0.82~1.64)0.395
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Toll样受体基因组特征与直肠癌临床病理及免疫参数的相关性分析
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李昂 1, 2 , 仵红娇 2 , 谢俞宁 1 , 贾祯贤 1 , 李佳莹 1 , 张雪梅 2, *
解放军医学杂志 | 临床研究 2021,46(4): 340-347
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解放军医学杂志 | 临床研究 2021, 46(4): 340-347
Toll样受体基因组特征与直肠癌临床病理及免疫参数的相关性分析
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李昂1, 2, 仵红娇2, 谢俞宁1, 贾祯贤1, 李佳莹1, 张雪梅2, *
作者信息
  • 1华北理工大学公共卫生学院，河北 唐山 063210
  • 2华北理工大学生命科学学院，河北 唐山 063210

    • 李昂，硕士研究生，主要从事分子肿瘤学方面的研究

通讯作者:

张雪梅，E-mail：
Correlation analysis between Toll-like receptor genomic characteristics and clinicopathological and immune parameters in rectal cancer
Ang Li1, 2, Hong-Jiao Wu2, Yu-Ning Xie1, Zhen-Xian Jia1, Jia-Ying Li1, Xue-Mei Zhang2, *
Affiliations
  • 1School of Public Health, North China University of Science and Technology, Tangshan, Hebei 063210, China
  • 2College of Life Sciences, North China University of Science and Technology, Tangshan, Hebei 063210, China
出版时间: 2021-04-28 doi: 10.11855/j.issn.0577-7402.2021.04.04
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摘要
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目的 探讨Toll样受体家族成员对直肠癌发生、预后和免疫特征的影响，以及其基因调节区遗传变异与直肠癌发病风险的关系。方法 使用GEPIA平台分析Toll样受体3(TLR3)、TLR4、TLR5和TLR7在直肠癌中的表达及其与预后的关系。从TCGA数据库获取直肠癌mRNA转录组数据和临床资料，分析TLR3表达与病理分期的关系。使用PCR-RFLP技术对TLR4 rs1927914、rs7869402多态进行基因分型，使用TaqMan探针法对TLR3 rs5743303、TLR5 rs1640816、TLR7 rs7869402多态进行基因分型。应用非条件logistic回归分析TLRs遗传变异与直肠癌发病风险的关系。使用ESTIMATE对直肠癌样本的免疫细胞进行评分，通过TIMER在线数据平台分析TLR3表达及拷贝数变异(CNV)与免疫细胞浸润的关系。GO功能富集分析TLR3相关差异基因的表达，基因集变异分析(GSVA)预测直肠癌中TLR3的调控网络。结果 TLR3在直肠癌组织中呈低表达，且其低表达与预后不良有关。与TLR3 rs5743303 AA基因型相比，AT或TT基因型携带者的直肠癌发病风险明显升高(OR=1.43，95%CI 1.07~1.91)。TLR4 rs1927914、TLR4 rs7869402、TLR5 rs1640816及TLR7 rs3853839多态不影响直肠癌的发病风险。分层分析结果显示，TLR3 rs5743303 AT或TT基因型可增加男性(OR=1.47，95%CI 1.01~2.11)、低年龄者(OR=1.64，95%CI 1.08~2.47)、吸烟者(OR=2.42，95%CI 1.37~4.38)和饮酒者(OR=2.70，95%CI 1.52~4.80)直肠癌的发病风险。ESTIMATE和TIMER分析结果显示，TLR3与免疫细胞浸润具有一定相关性。GO功能富集分析结果显示，TLR3主要与受体配体活性、抗原结合、免疫球蛋白受体结合、生长因子和细胞因子等相关功能的改变有关。GSVA分析结果显示，TLR3可通过调节细胞凋亡、自然杀伤细胞介导的细胞毒性、磷脂代谢及自噬调节等与代谢或免疫相关的途径而抑制直肠癌的发生发展。结论 TLR3与直肠癌的发生及预后相关，TLR3 rs5743303遗传变异可影响直肠癌的遗传易感性。

Toll样受体  /  单核苷酸多态性  /  免疫  /  直肠癌

Objective To investigate the effects of Toll-like receptors (TLR3/TLR4/TLR5/TLR7) on the development, prognosis and immune characteristics of rectal cancer and to explore the association of genetic variation in the regulation region of TLRs with the risk for rectal cancer. Methods Gene expression profiling interactive analysis (GEPIA) platform was used to analyze the expression of TLRs in rectal cancer and its relationship with prognosis. Transcriptome data and clinical data of rectal cancer were downloaded from TCGA database and the correlation between TLRs expression and pathological stage was analyzed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of TLR4 rs1927914 and rs7869402 polymorphism. TaqMan probe method was used to determine the genotypes of TLR3 rs5743303, TLR5 rs1640816 and TLR7 rs7869402 variants. The association of TLRs genetic variants with the rectal cancer risk was analyzed by unconditional logistic regression. The immune cells in rectal cancer samples were scored using ESTIMATE algorithm. Using TIMER online data platform, the relationship between both the expression of TLRs and copy number variation (CNV) of genes and immune infiltrated cells was evaluated. Gene function related to TLR3 expression was evaluated by GO function enrichment analysis, gene set variation analysis(GSVA) was used to predict the regulatory network of TLR3 in rectal cancer. Results TLR3 has a lower expression in rectal cancer tissues than in adjacent tissues, which was related to poor prognosis. Compared with the individuals carrying TLR3 AA genotype, the individuals with at least one TLR3 rs5743303 T allele had significantly higher risk of rectal cancer (OR=1.43, 95%CI 1.07-1.91).The study did not show that TLR4 rs1927914, TLR4 rs7869402, TLR5 rs1640816 and TLR7 rs3853839 polymorphism had effect on the risk for rectal cancer. After stratified analysis, the data showed that TLR3 rs5743303 AT or TT contributed the susceptibility to rectal cancer in males (OR=1.47, 95%CI 1.01-2.11), younger subjects (OR=1.64, 95%CI 1.08-2.47), smokers (OR=2.42, 95%CI 1.37-4.38) and drinkers (OR=2.70, 95%CI 1.52-4.80). ESTIMATE and TIMER analyses showed that TLR3 effected on the immune cell infiltration. The results of GO functional enrichment analysis showed that TLR3 was mainly related to changes in related functions such as receptor ligand activity, antigen binding, immunoglobulin receptor binding, growth factors and cytokines. GSVA results showed that TLR3 inhibited the development of rectal cancer by regulating metabolic or immune-related pathways, such as cell apoptosis, natural killer cell-mediated cytotoxicity, phospholipid metabolism and autophagy regulation. Conclusion TLR3 effects on the occurrence and prognosis of rectal cancer and rs5743303 polymorphism increase the susceptibility to rectal cancer.

Toll-like receptor  /  single nucleotide polymorphism  /  immunity  /  rectal cancer
李昂, 仵红娇, 谢俞宁, 贾祯贤, 李佳莹, 张雪梅. Toll样受体基因组特征与直肠癌临床病理及免疫参数的相关性分析. 解放军医学杂志, 2021 , 46 (4) : 340 -347 . DOI: 10.11855/j.issn.0577-7402.2021.04.04
Ang Li, Hong-Jiao Wu, Yu-Ning Xie, Zhen-Xian Jia, Jia-Ying Li, Xue-Mei Zhang. Correlation analysis between Toll-like receptor genomic characteristics and clinicopathological and immune parameters in rectal cancer[J]. Medical Journal of Chinese People’s Liberation Army, 2021 , 46 (4) : 340 -347 . DOI: 10.11855/j.issn.0577-7402.2021.04.04
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结直肠癌(colorectal cancer，CRC)是世界上第三大常见癌症，也是导致癌症患者死亡的第二大原因[1]。美国癌症协会的流行病学调查显示，直肠癌在CRC中占比达35%。作为先天免疫的重要组成部分，炎症是癌症发生和进展的标志性特征[2]。Toll样受体(Toll like receptors，TLRs)是特殊的模式识别受体(pattern recognition receptors，PRRs)，可诱导免疫细胞表面相关分子的表达而激活免疫应答途径，还可与相应配体结合激活炎症通路[3]。据统计，除环境危险因素(包括肥胖、缺乏运动、不良饮食、饮酒和吸烟)外，1/3的直肠癌是由遗传因素诱导发生的[4-5]，而单核苷酸多态性(single nucleotide polymorphism，SNP)在人类的可遗传变异中较为常见。调节区和3'非翻译区SNP可分别通过调节与转录因子或miRNA的结合，从而对靶基因调控产生影响[6]。因此，具有潜在功能的SNP可能会增加机体对癌症的易感性。有研究发现，TLR3调控区基因多态性与肠道病毒71型(EV71)重症感染的易感性相关[7]，而肠道感染也是CRC的诱因之一[8]。鉴于TLRs在肿瘤中的重要作用，本研究通过查阅文献并利用生物信息学方法筛选出5个潜在的功能SNP位点，探讨其对CRC发病风险的影响，以期为CRC的防治及早期诊断提供理论依据。
1 资料与方法
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1.1 研究对象
本研究采用病例对照的研究策略。选取2008—2016年在华北理工大学附属唐山市工人医院和华北理工大学附属唐山市人民医院住院治疗的480例经组织病理学确诊且采血前未接受放化疗的原发性直肠癌患者设为病例组，另随机选取同期在唐山地区进行体检的480名健康者设为对照组，排除与病例组有血缘关系、有肿瘤家族史、接受放射治疗或者抗癌化学药物治疗的个体。本研究经华北理工大学伦理审查委员会批准(2019021)，所有参与者均签署知情同意书。
1.2 SNP筛选
从dbSNP及Ensembl数据库中提取TLR家族成员基因多态数据信息，筛选位于启动子区及3'非翻译区且在中国汉族人群中最小等位基因频率>0.05的遗传变异。使用TRANSFAC和SNPinfo Web Serve软件分别对筛选出的SNP进行转录因子结合和miRNA结合能力预测，最终确定研究位于启动子区的TLR3 rs5743303、TLR4 rs1927914、TLR5 rs1640816，以及3'非翻译区的TLR4 rs7869402、TLR7 rs3853839多态。
1.3 基因分型
使用DNA提取试剂盒(北京天根生化科技有限公司)提取外周血DNA。针对TLR3 rs5743303、TLR5 rs1640816和TLR7 rs3853839多态，使用TaqMan探针法进行基因分型。PCR反应体系包括1×Taq PCR MasterMix Ⅱ(美国ABI公司)2 μl、探针0.065 μl和基因组DNA 1 μl(>10 ng)，最后用双蒸水补至5 μl，使用ABI 7900HT Fast Real-Time PCR system进行检测。针对TLR4 rs1927914和rs7869402多态，使用聚合酶链反应限制性片段长度多态性(PCR-RFLP)技术进行基因分型。引物序列如下：TLR4 rs1927914上游5'-TAGCATGAGA AATGAGGAAGTAAGGG-3'，下游5'-GAGCTATG ATGAGGATTGAAAATGTGG-3'；TLR4 rs7869402上游5'TGGGATCCCTCCCCTGTAGC-3'，下游5'-AGGAGCATTGCCCAACAGG-3'。PCR反应体系包括上下游引物各0.1 μl(10 mmol/L)，cDNA 1 μl(>10 ng)，2×Taq PCR Starmix 3 μl(北京康润诚业生物科技有限公司)，最后用双蒸水补至6 μl。PCR扩增条件：94℃预变性3 min；94℃变性30 s，58℃退火30 s，72℃延伸30 s，进行30个循环；然后72℃延伸5 min。使用AluⅠ和NsiⅠ限制性核酸内切酶(NEB公司)对TLR4 rs1927914和rs7869402的PCR产物进行酶切。酶切产物经2.5%琼脂糖凝胶电泳进行基因型判断。为提高基因分型的准确度，随机选取10%的样本进行重复实验，结果一致。
1.4 统计学处理
利用GEPIA在线数据平台分析直肠癌中TLRs的表达及其与直肠癌预后的相关性，ESTIMATE算法分析TLR3表达与免疫细胞评分的相关性，TIMER数据库评估直肠癌TLR3表达及拷贝数变异与免疫细胞浸润的相关性。从TCGA数据库获取直肠癌患者的转录组数据和临床信息，利用WilcoxTest函数评估TLRs基因表达与病理分期的关系，KEGG通路和GO功能富集分析TLR3相关差异基因的表达[利用R语言中的基因集变异分析(GSVA)软件包完成]。采用SPSS 23.0软件进行统计分析。采用χ2检验比较病例组与对照组研究对象的基本特征及基因型分布的差异，非条件logistic回归分析TLRs遗传变异与直肠癌发病风险的关系。所有统计检验均为双侧概率检验，P<0.05为差异有统计学意义。
2 结果
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2.1 TLRs与直肠癌临床病理的关系
GEPIA在线数据平台分析结果显示，TLR3在直肠癌组织中的表达明显低于正常组织(P<0.05)，且其低表达与预后不良相关(HR=0.26，95%CI 0.094~0.87，P=0.021)。TLR4、TLR5和TLR7在直肠癌组织与正常组织中的表达差异无统计学意义，且与直肠癌预后无关(P>0.05)。TLRs的表达与直肠癌临床病理分期无相关性(P>0.05)(图1)。
2.2 TLRs遗传变异与直肠癌易感性的关系
两组年龄中位数均为60岁，年龄、性别以及吸烟和饮酒占比等基本资料比较，差异无统计学意义(P>0.05，表1)。
TLRs遗传变异各基因型分布与直肠癌易感性的关系如表2所示。病例组TLR3 rs5743303 AA、AT和TT基因型频率分别为69.8%(335/480)、26.7%(128/480)和3.5%(17/480)，对照组分别为76.7%(368/480)、20.8%(100/480)和2.5%(12/480)。非条件logistic回归分析结果显示，与TLR3 rs5743303 AA基因型相比，AT或TT基因型携带者的直肠癌发病风险明显增加(OR=1.43，95%CI 1.07~1.90)。而TLR4 rs1927914、TLR4 rs7869402、TLR5 rs1640816和TLR7 rs3853839遗传变异并不影响直肠癌的发病风险(P>0.05)。
TLR3 rs5743303遗传变异与直肠癌发病风险的分层分析结果如表3所示。性别分层结果显示，男性AT或TT基因型携带者的直肠癌发病风险是AA基因型携带者的1.47倍(P=0.041)，在女性中未见该变异影响直肠癌发病风险(P=0.202)。年龄分层结果显示，低年龄(≤60岁)AT或TT基因型携带者发生直肠癌的风险较高(OR=1.64，95% CI 1.08~2.47，P=0.019)，而在高龄(>60岁)者中差异无统计学意义(P=0.185)。吸烟和饮酒分层结果显示，与AA基因型携带者相比，携带AT或TT基因型的吸烟者(OR=2.42，95% CI 1.37~4.38)和饮酒者(OR=2.70，95% CI 1.52~4.80)发生直肠癌的风险较高(P=0.002，P=0.001)。
2.3 TLR3与免疫特征参数的关系
ESTIMATE算法分析结果显示，TLR3表达与直肠癌免疫评分呈正相关(r=0.23，P=0.038，图2A)。TIMER数据库分析结果显示，TLR3表达与CD8+ T细胞的相关性最强(r=0.537，P<0.001)，与巨噬细胞无相关性(r=0.008，P=0.921，图2C)；体细胞TLR3拷贝数变异与B细胞、CD8+ T细胞、CD4+ T细胞、巨噬细胞、中性粒细胞和树突细胞的浸润程度呈弱相关或无相关性(P<0.05，图2B)。
2.4 直肠癌中TLR3的GO功能和GSVA富集分析
对TCGA数据库中直肠癌的RNA测序数据进行GO功能分析，结果显示，TLR3高表达主要与受体配体活性、抗原结合、免疫球蛋白受体结合、生长因子和细胞因子等相关基因功能的改变有关(图3A)。GSVA富集分析结果显示，TLR3相关通路主要富集在细胞凋亡、自然杀伤细胞介导的细胞毒性、磷脂代谢及自噬调节等与代谢或免疫相关的途径(图3B)。
3 讨论
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直肠癌是消化系统常见的恶性肿瘤之一。我国癌症统计数据显示，国人直肠癌发病率逐年上升且呈年轻化趋势[9]。尽管手术、靶向治疗及放化疗已在直肠癌的治疗中取得了满意的疗效，但患者5年总体生存率仍较低[10]。因此，对直肠癌发病及预后的影响因素进行探索，以发现直肠癌易感因素及预后因素，有助于改善直肠癌患者的生存质量及预后情况。
TLRs是特殊的模式识别受体，可通过参与不同的病原相关分子模式(pathogen-associated molecular patterns，PAMP)和损伤相关分子模式(damage associated molecular patterns，DAMP)引起促炎因子、趋化因子和干扰素的释放而激活炎症通路，进而启动免疫反应[11]。TLRs可增加血管通透性，也可通过细胞毒性T细胞和自然杀伤细胞杀伤肿瘤细胞，从而发挥抑制肿瘤的作用[12]。在免疫治疗时代，肿瘤的发展受其内在特征及外在肿瘤微环境的共同影响。TLRs活化后经信号转导产生炎性因子并激活树突细胞[13]，而位于肿瘤微环境中的树突细胞可发挥抗原提呈作用，使自然杀伤细胞和T细胞活化，从而发挥细胞毒性作用，进而抑制肿瘤的发生发展[14]。
Bonnin等[15]发现，TLR3 mRNA及蛋白在肝癌组织中的表达均低于癌旁组织，且TLR3表达下调与肝癌患者生存率降低有关。对神经母细胞瘤和食管癌的研究发现，肿瘤实质中TLR3高表达与预后良好相关[16-17]，在非小细胞肺癌早期，TLR3高表达具有抑癌作用且与较高的总体生存率明显相关[18]。TLR3激动剂是一种强效免疫调节剂，可通过激活TLR3的表达来刺激抗原呈递细胞，从而活化肿瘤特异性T细胞，以及将骨髓抑制细胞和肿瘤相关巨噬细胞的表型从免疫抑制转为免疫支持[19-21]。本研究生物信息学分析结果显示，先天免疫基因TLR3在直肠癌中低表达且与预后不良有关。肿瘤基因表达谱可以量化肿瘤微环境中的免疫活性[22]。本研究通过ESTIMATE和TIMER分析发现，TLR3与肿瘤微环境中的免疫细胞浸润具有一定的相关性，且GSVA富集分析结果也显示TLR3低表达可抑制自然杀伤细胞介导的细胞毒性通路，从而发挥促进肿瘤发展的作用。
TLRs基因中存在的SNP可能会损害其功能并破坏促炎与抗炎细胞因子之间的平衡，增加慢性炎症和癌症的发生风险[23-25]。TLR3 SNP影响癌症易感性，可作为评估癌症发生风险的潜在生物标志物[26]。与野生型相比，TLR3突变型与口腔癌和鼻咽癌的发病风险明显相关[27]。虽有研究表明TLR3基因多态性与乳腺癌的发病风险无关，但TLR3的表达与乳腺癌的侵袭性有关[28]。迄今为止，关于TLR3 SNP与直肠癌易感性关系的报道较少。本研究结果显示，TLR3低表达是直肠癌的危险因素，且TLR3 rs5743303的遗传变异与直肠癌发病风险增加明显相关，但直肠癌中TLR3 rs5743303遗传变异是否导致基因差异表达，尚需进一步研究验证。
既往研究发现，SNP可能通过破坏TLR4信号转导而增加慢性炎症和癌症的发生风险[29]，但尚未发现TLR4 rs1927914遗传变异与肺癌[30]、前列腺癌[31]、肝细胞癌[32]和胃癌[33]之间有任何明显关联。本研究亦未发现TLR4 rs1927914遗传变异与直肠癌发病风险有关。据报道，TLR5在多种癌症中表达并在癌变中起作用[34-36]。Chen等[37]发现，TLR5遗传变异与人类乳腺癌易感性存在密切关系。与其他TLR家族成员不同，TLR5在肠道上皮细胞中高度表达，并在宿主抵抗肠道细菌感染中发挥关键作用[38]。本研究结果显示，TLR5 rs1640816遗传变异与直肠癌发病风险无相关性。有研究发现，炎症性肠病患者与对照组TLR7 rs3853839等位基因频率无明显差异[39]。本研究亦未发现TLR7 rs3853839 G>C多态性与直肠癌发病风险有任何关联。
除遗传因素外，肿瘤的发生也与环境因素有关。流行病学研究表明，吸烟可能诱发表观遗传改变[40-41]，是直肠癌发病的适度危险因素[42-43]。本研究结果显示，至少携带一个TLR3 rs5743303 T等位基因的男性和低年龄者具有较高的直肠癌发病风险，且吸烟、饮酒可增加个体罹患直肠癌的风险，提示直肠癌的发生主要是环境因素和遗传因素共同作用的结果。
综上所述，本研究结果表明，TLR3低表达可能通过抑制免疫细胞活性及免疫相关途径促进直肠癌的发生与不良预后，且TLR3遗传变异可能增加个体罹患直肠癌的风险，但其具体作用机制尚需进一步研究证实。
基金
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  • 国家自然科学基金(81101483)
  • 河北省自然科学基金(H2017209233)
文献
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参考文献 引证文献
排序方式：
[1]
Siegel RL, Miller KD, Goding Sauer A, et al. Colorectal cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(3): 145-164.
[2]
Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation[J]. Cell, 2011, 144(5): 646-674.
[3]
Bao LL, Cui LH. Exprossion of TLR4 and NF-κB in rats model induced with IBS-D and its mechanism[J]. Med J Chin PLA, 2019, 44(8): 648-651.
[鲍璐璐, 崔立红. IBS-D大鼠结肠TLR4、NF-κB的表达变化及机制[J]. 解放军医学杂志, 2019, 44(8): 648-651.]
[4]
Lichtenstein P, Holm NV, Verkasalo PK, et al. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland[J]. N Engl J Med, 2000, 343(2): 78-85.
[5]
Kory WJ, Thérèse MT, Deborah WN, et al. Hereditary and familial colon cancer[J]. Gastroenterology, 2010, 138(6): 2044-2058.
[6]
Trejo-de la OA, Hernández-Sancén P, Maldonado-Bernal C.Relevance of single-nucleotide polymorphisms in human TLR genes to infectious and inflammatory diseases and cancer[J]. Genes Immun, 2014, 15(4): 199-209.
[7]
He H, Liu S, Liu PP, et al. Association of Toll-like receptor 3 gene polymorphism with the severity of enterovirus 71 infection in Chinese children[J]. Arch Virol, 2017, 162(6): 1717-1723.
[8]
He YT, Liu L. Relationship between the gut microbiome and the development of colorectal cancer[J]. New Medicine, 2020, 30(6): 464-470.
[何杨婷, 刘莉. 肠道菌群与结直肠癌发生发展的关系[J]. 医学新知, 2020, 30(6): 464-470.]
[9]
Gong J, Yuan GP, Lin YJ, et al. Outcomes of high risk assessment and clinical screening on cancer among community residents in Jiangbei district of Ningbo city: 2013-2017[J]. Chin J Publ Heal, 2019, 35(11): 1572-1574.
[龚静, 元国平, 林寅君, 等. 宁波市江北区2013－2017年度居民癌症高风险评估及临床筛查结果分析[J]. 中国公共卫生, 2019, 35(11): 1572-1574.]
[10]
Huh JW, Kim HC, Kim SH, et al. Mismatch repair gene expression as a predictor of tumor responses in patients with rectal cancer treated with preoperative chemoradiation[J]. Medicine (Baltimore), 2016, 95(3): e2582.
[11]
Vijay K. Toll-like receptors in immunity and inflammatory diseases: Past, present, and future[J]. Int Immunopharmacol, 2018, 59: 391-412.
[12]
Bellmann L, Cappellano G, Schachtl-Riess JF, et al. A TLR7 agonist strengthens T and NK cell function during BRAF-targeted therapy in a preclinical melanoma model[J]. Int J Cancer, 2020, 146(5): 1409-1420.
[13]
McCall KD, Muccioli M, Benencia F. Toll-like receptors signaling in the tumor microenvironment[J]. Adv Exp Med Biol, 2020, 1223: 81-97.
[14]
Pulko V, Liu X, Krco CJ, et al. TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination[J]. J Immunol, 2009, 183(6): 3634-3641.
[15]
Bonnin M, Fares N, Testoni B, et al. Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis[J]. J Hepatol, 2019, 71(4): 763-772.
[16]
Bianchi F, Pretto S, Tagliabue E, et al. Exploiting poly(I: C) to induce cancer cell apoptosis[J]. Cancer Biol Ther, 2017, 18(10): 747-756.
[17]
Sato Y, Motoyama S, Wakita A, et al. TLR3 expression status predicts prognosis in patients with advanced thoracic esophageal squamous cell carcinoma after esophagectomy[J]. Am J Surg, 2018, 216(2): 319-325.
[18]
Bianchi F, Milione M, Casalini P, et al. Toll-like receptor 3 as a new marker to detect high risk early stage non-small-cell lung cancer patients[J]. Sci Rep, 2019, 9(1): 14288.
[19]
Le Noci V, Tortoreto M, Gulino A, et al. Poly(I: C) and CpG-ODN combined aerosolization to treat lung metastases and counter the immunosuppressive microenvironment[J]. Oncoimmunology, 2015, 4(10): e1040214.
[20]
Le Noci V, Sommariva M, Tortoreto M, et al. Reprogramming the lung microenvironment by inhaled immunotherapy fosters immune destruction of tumor[J]. Oncoimmunology, 2016, 5(11): e1234571.
[21]
Shime H, Matsumoto M, Oshiumi H, et al. Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors[J]. Proc Natl Acad Sci U S A, 2012, 109(6): 2066-2071.
[22]
Sweis RF, Spranger S, Bao R, et al. Molecular drivers of the non-T-cell-inflamed tumor microenvironment in urothelial bladder cancer[J]. Cancer Immunol Res, 2016, 4(7): 563-568.
[23]
Yang ZH, Dai Q, Gu YJ, et al. Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma[J]. Cancer Sci, 2012, 103(4): 653-658.
[24]
Kutikhin AG, Yuzhalin AE. Are Toll-like receptor gene polymorphisms associated with prostate cancer?[J]. Cancer Manag Res, 2012, 4: 23-29.
[25]
Joosten LA, Abdollahi-Roodsaz S, Dinarello CA, et al. Toll-like receptors and chronic inflammation in rheumatic diseases: new developments[J]. Nat Rev Rheumatol, 2016, 12(6): 344-357.
[26]
Netea MG, Wijmenga C, O'Neill LAG. Genetic variation in Toll-like receptors and disease susceptibility[J]. Nat Immunol, 2012, 13(6): 535-542.
[27]
Zeljic K, Supic G, Jovic N, et al. Association of TLR2, TLR3, TLR4 and CD14 genes polymorphisms with oral cancer risk and survival[J]. Oral Dis, 2014, 20(4): 416-424.
[28]
Fan L, Zhou P, Hong Q, et al. Toll-like receptor 3 acts as a suppressor gene in breast cancer initiation and progression: A two-stage association study and functional investigation[J]. Oncoimmunology, 2019, 8(6): e1593801.
[29]
Kutikhin AG. Impact of Toll-like receptor 4 polymorphisms on risk of cancer[J]. Hum Immunol, 2011, 72(2): 193-206.
[30]
Hart K, Landvik NE, Lind H, et al. A combination of functional polymorphisms in the CASP8, MMP1, IL10 and SEPS1 genes affects risk of non-small cell lung cancer[J]. Lung Cancer, 2011, 71(2): 123-129.
[31]
Song J, Kim DY, Kim CS, et al. The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of prostate cancer in Korean men[J]. Cancer Genet Cytogenet, 2009, 190(2): 88-92.
[32]
Shi M, Xu X, Chen H, et al. Single nucleotide polymorphisms of Toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma[J]. PLoS One, 2011, 6(4): e19466.
[33]
Huang H, Wu J, Jin G, et al. A 5'-flanking region polymorphism in toll-like receptor 4 is associated with gastric cancer in a Chinese population[J]. J Biomed Res, 2010, 24(2): 100-106.
[34]
Pimentel-Nunes P, Afonso L, Lopes P, et al. Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia[J]. Pathol Oncol Res, 2011, 17(3): 677-683.
[35]
Kauppila JH, Mattila AE, Karttunen TJ, et al. Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue[J]. Br J Cancer, 2013, 108(3): 638-643.
[36]
Pinto A, Morello S, Sorrentino R. Lung cancer and Toll-like receptors[J]. Cancer Immunol Immunother, 2011, 60(9): 1211-1220.
[37]
Chen S, Yuan W, Fu Z, et al. Toll-like receptor 5 gene polymorphism is associated with breast cancer susceptibility[J]. Oncotarget, 2017, 8(51): 88622-88629.
[38]
Uematsu S, Akira S. Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection[J]. J Gastroenterol, 2009, 44(8): 803-811.
[39]
Yang JY, Kim MS, Kim E, et al. Enteric viruses ameliorate gut inflammation via Toll-like receptor 3 and Toll-like receptor 7-mediated interferon-β production[J]. Immunity, 2016, 44(4): 889-900.
[40]
Gao X, Zhang Y, Breitling LP, et al. Tobacco smoking and methylation of genes related to lung cancer development[J]. Oncotarget, 2016, 7(37): 59017-59028.
[41]
Gao X, Jia M, Zhang Y, et al. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: A systematic review of DNA methylation studies[J]. Clin Epigenetics, 2015, 7: 113.
[42]
Cheng J, Chen Y, Wang X, et al. Meta-analysis of prospective cohort studies of cigarette smoking and the incidence of colon and rectal cancers[J]. Eur J Cancer Prev, 2015, 24(1): 6-15.
[43]
Fagunwa IO, Loughrey MB, Coleman HG. Alcohol, smoking and the risk of premalignant and malignant colorectal neoplasms[J]. Best Pract Res Clin Gastroenterol, 2017, 31(5): 561-568.
2021年第46卷第4期
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doi: 10.11855/j.issn.0577-7402.2021.04.04
  • 接收时间：2020-04-27
  • 首发时间：2025-12-26
  • 出版时间：2021-04-28
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  • 收稿日期：2020-04-27
  • 修回日期：2021-02-16
基金
National Natural Science Foundation of China(81101483)
国家自然科学基金(81101483)
Natural Science Foundation of Hebei Province(H2017209233)
河北省自然科学基金(H2017209233)
作者信息
    1华北理工大学公共卫生学院，河北 唐山 063210
    2华北理工大学生命科学学院，河北 唐山 063210

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张雪梅，E-mail：
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2种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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