Article(id=1208055576244883799, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208055572495179979, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2022.06.0586, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1624291200000, receivedDateStr=2021-06-22, revisedDate=null, revisedDateStr=null, acceptedDate=1630857600000, acceptedDateStr=2021-09-06, onlineDate=1765952493963, onlineDateStr=2025-12-17, pubDate=1656345600000, pubDateStr=2022-06-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1765952493963, onlineIssueDateStr=2025-12-17, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1765952493963, creator=13701087609, updateTime=1765952493963, updator=13701087609, issue=Issue{id=1208055572495179979, tenantId=1146029695717560320, journalId=1189873630562394117, year='2022', volume='47', issue='6', pageStart='533', pageEnd='638', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1765952493070, creator=13701087609, updateTime=1765952764848, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1208056712481841868, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208055572495179979, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1208056712481841869, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1208055572495179979, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=586, endPage=592, ext={EN=ArticleExt(id=1208055577570283878, articleId=1208055576244883799, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Expression of serum exosomes integrins and their clinical significance in patients with colorectal cancer, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the expression levels of serum exosomes integrin α₅, β₅ and β₆ and their clinical significance in patients with different stages of colorectal cancer (CRC). Methods The serum samples were collected from 50 patients with CRC admitted in the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine and Hunan Cancer Hospital from January 2016 to October 2020, and were divided into CRC stage Ⅰ group (n=5), CRC stage Ⅱ group (n=19), CRC stage Ⅲ group (n=14), and CRC stage Ⅳ group (only liver metastasis, n=12) according the TNM stage. The serum samples were collected from 10 healthy people who underwent physical examination in the Health Management Center of the Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine from August 2018 to May 2020, and set as healthy people group. The exosomes were purified, and then identified by nanoparticle tracking assay (NTA) and Western blotting. The expression levels of integrin α₅,β₅ and β₆ were detected by Western blotting, the survival time of 50 patients with CRC were followed up. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazards model was used for survival analysis. Results The 50 patients with CRC [26 males (52.0%) and 24 females (48.0%)] are mainly middle- and elderly-aged with average age of 58 years. Five cases (10.0%)in TNM stage Ⅰ, 19 cases (38.0%) in stage Ⅱ, 14 cases (28.0%) in stage Ⅲ and 12 cases (24.0%) in stage Ⅳ (only liver metastasis).Up to February 2021, the follow-up time was 5-60 months, and the median follow-up time was 44 months, no cases fell off or lost follow-up. NTA analysis showed that the particle diameter of serum exosomes in all serum samples were concentrated in 50-150 nm.Western blotting results showed that the marker proteins of serum exosomes ALIX and HSP70 were expressed in all serum samples,which confirmed that these extracts were exosomes. Integrin α₅, β₅ and β₆ were expressed in different degrees, the expression levels of integrin α₅ and β₅ increased with the increase of TNM stage, and significantly higher in live metastasis than in non-stage Ⅳ(P<0.05). However, no significant relationship existed between the expression of integrin β₆ and TNM stage (P>0.05). Kaplan-Meier method showed that integrin α₅, β₅ and TNM stage were related with survival of patients with CRC (P<0.05). The results of Cox proportional risk model suggested that integrin α₅ and the degree of pathological differentiation were independent influencing factors of survival in patients with CRC (P<0.05). Conclusion Exosomes integrin α₅, β₅ are related to liver metastasis and TNM stage of CRC. Exosomes integrin α₅ and the degree of pathological differentiation are related to the prognosis of colorectal cancer,and integrin α₅ and β₅ may become potential serum markers.

, correspAuthors=Yi-Lan Jiang, authorNote=null, correspAuthorsNote=, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Jiao Jiao, Ji-Yun Tang, Jia-Qin Liu, Qi Tang, Dong-Fang Li, Guang-Sheng Hu, Yi-Lan Jiang), CN=ArticleExt(id=1208055579126370744, articleId=1208055576244883799, tenantId=1146029695717560320, journalId=1189873630562394117, language=CN, title=结直肠癌患者血清外泌体整合素的表达及其临床意义, columnId=1190310109164180259, journalTitle=解放军医学杂志, columnName=临床研究, runingTitle=null, highlight=null, articleAbstract=

目的 探讨不同分期结直肠癌患者血清外泌体中整合素α₅、β₅、β₆的表达水平及其临床意义。方法 收集2016年1月－2020年10月就诊于湖南省中医药研究院附属医院和湖南省肿瘤医院的50例结直肠癌患者的血清标本，按照TNM分期分为结直肠癌Ⅰ期组(n=5)、Ⅱ期组(n=19)、Ⅲ期组(n=14)与Ⅳ期组(仅肝转移，n=12)。另收集2018年8月－2020年5月于湖南省中医药研究院附属医院健康管理中心体检的10名健康者的血清标本作为健康对照组。对血清标本进行外泌体提纯，运用纳米微粒追踪分析(NTA)及Western blotting鉴定外泌体；采用Western blotting检测血清外泌体中整合素α₅、β₅、β₆的表达水平。随访追踪50例结直肠癌患者的生存期，采用Kaplan-Meier法绘制生存曲线，采用Cox比例风险回归模型进行生存分析。结果 50例结直肠癌患者中，男26例(52.0%)，女24例(48.0%)，以中老年群体为主，平均年龄58岁；TNM分期Ⅰ期5例(10.0%)，Ⅱ期19例(38.0%)，Ⅲ期14例(28.0%)，Ⅳ期(仅肝转移) 12例(24.0%)。随访截至2021年2月，随访时间5~60个月，中位随访时间44个月，无病例脱落或失访。NTA分析结果显示，各组血清外泌体的粒径分布集中在50~150 nm。Western blotting检测结果显示，各组血清外泌体中ALIX、HSP70等标志性蛋白均有表达，证实提取物为外泌体；各组血清外泌体中整合素α₅、β₅、β₆均有不同程度表达，其中整合素α₅、β₅的表达水平随着TNM分期增加而升高，肝转移Ⅳ期患者α₅、β₅表达水平明显高于非Ⅳ期患者(P<0.05)，而整合素β₆表达与TNM分期无明显关系(P>0.05)。Kaplan-Meier生存曲线分析显示，整合素α₅、β₅及TNM分期与结直肠癌患者的生存期有关(P<0.05)；Cox比例风险回归模型分析结果显示，整合素α₅及病理分化程度是结直肠癌患者生存期的独立影响因素(P<0.05)。结论 外泌体整合素α₅、β₅与结肠癌肝转移及TNM分期有关，外泌体整合素α₅及病理分化程度与结肠癌预后有关，外泌体整合素α₅、β₅可能成为潜在的血清标志物。

, correspAuthors=蒋益兰, authorNote=null, correspAuthorsNote=, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=edktajvAHalInpji6Ey44g==, magXml=mrCVJBIrSZ37CIC3rI6atA==, pdfUrl=null, pdf=v/a/qALc+95+A+g/iDJICg==, pdfFileSize=1224700, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=hhCzlalwozKMjEZOPF/O6A==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=5VgiQri1fLYY9OCPRl876A==, mapNumber=null, authorCompany=null, fund=null, authors=, authorsList=焦蕉, 唐继云, 刘佳琴, 唐麒, 李东芳, 胡广生, 蒋益兰)}, authors=[Author(id=1208063096686481591, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1208063096761979069, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, authorId=1208063096686481591, language=EN, stringName=Jiao Jiao, firstName=Jiao, middleName=null, lastName=Jiao, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^{1, 2}, address=¹Department of Integrated Chinese and Western Medicine, Hunan Cancer Hospital, Changsha 410013, China
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焦蕉，硕士研究生，主治医师，从事中西医结合防治恶性肿瘤方面的研究

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焦蕉，硕士研究生，主治医师，从事中西医结合防治恶性肿瘤方面的研究

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tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=CN, label=图1, caption=各组血清外泌体纳米微粒追踪分析(NTA)结果

A. 健康对照组；B. 结直肠癌Ⅰ期组；C. 结直肠癌Ⅱ期组；D. 结直肠癌Ⅲ期组；E. 结直肠癌Ⅳ期组

, figureFileSmall=Xntt/C8ATXi06Chathx88w==, figureFileBig=Ww+VcMIj1J619SObGiUYcQ==, tableContent=null), ArticleFig(id=1208063100822065439, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=EN, label=Fig.2, caption=Expression of serum exosomes marker proteins ALIX and HSP70 in each group (Western blotting), figureFileSmall=OORs5+JghnufntwjcEjnaA==, figureFileBig=j+Tmc3bSJ8QnLdHzcVqEDA==, tableContent=null), ArticleFig(id=1208063100876591393, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=CN, label=图2, caption=各组血清外泌体标志蛋白ALIX、HSP70的表达情况(Western blotting), figureFileSmall=OORs5+JghnufntwjcEjnaA==, figureFileBig=j+Tmc3bSJ8QnLdHzcVqEDA==, tableContent=null), ArticleFig(id=1208063100935311653, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=EN, label=Fig.3, caption=Expression of integrin α₅, β₅ and β₆ in serum exosomes of each group (Western blotting), figureFileSmall=oBGKug3pUocmkViWzEUqGg==, figureFileBig=obwWB9/ZS+kJ3QTsRmfHdQ==, tableContent=null), ArticleFig(id=1208063101002420517, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=CN, label=图3, caption=各组血清外泌体中整合素α₅、β₅、β₆的表达情况(Western blotting)

与健康对照组比较，(1)P<0.01；与结直肠癌Ⅰ期组比较，(2)P<0.05，(3)P<0.01；与结直肠癌Ⅱ期组比较，(4)P<0.01；与结直肠癌Ⅲ期组比较，(5)P<0.01

, figureFileSmall=oBGKug3pUocmkViWzEUqGg==, figureFileBig=obwWB9/ZS+kJ3QTsRmfHdQ==, tableContent=null), ArticleFig(id=1208063101073723686, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=EN, label=Fig.4, caption=Kaplan-Meier curve analysis of the influencing factors of survival of patients with colorectal cancer, figureFileSmall=GaWPeSXDniKx2Mu9GPdhgg==, figureFileBig=I8O1MJmy2y9G5h6s10RjNQ==, tableContent=null), ArticleFig(id=1208063101161804073, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=CN, label=图4, caption=结直肠癌患者生存期影响因素的Kaplan-Meier曲线分析, figureFileSmall=GaWPeSXDniKx2Mu9GPdhgg==, figureFileBig=I8O1MJmy2y9G5h6s10RjNQ==, tableContent=null), ArticleFig(id=1208063101266661675, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=EN, label=Fig.5, caption=Multivariate Cox proportional hazards model of integrin α₅ and the degree of pathological differentiation, figureFileSmall=wmElwPSFWLlxdjKUL5nHkw==, figureFileBig=5Rfx1wiSZK2Xly4Tfr0cWA==, tableContent=null), ArticleFig(id=1208063101354742060, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=CN, label=图5, caption=基于整合素α₅、病理分化程度的Cox比例风险回归模型

Cox比例风险回归方程：h(t, X)=h0(t)exp(–2.925×整合素α₅+1.202病理分化程度)。整合素α₅：1=低值，2=中值，3=高值；病理分化程度：1=高分化，2=中分化，3=低分化及黏液性腺癌

, figureFileSmall=wmElwPSFWLlxdjKUL5nHkw==, figureFileBig=5Rfx1wiSZK2Xly4Tfr0cWA==, tableContent=null), ArticleFig(id=1208063101438628141, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1208055576244883799, language=EN, label=Tab.1, caption=

Multivariate Cox proportional hazards model analysis of the influencing factors of survival of patients with colorectal cancer

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因素	β	SE	Wald χ2	df	P	OR	95%CI
病理分化程度	1.202	0.489	6.059	1	0.014	3.328	1.278~8.671
整合素α5	2.925	0.738	15.686	1	0.000	18.626	4.381~79.191

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结直肠癌患者生存期影响因素的Cox比例风险回归模型分析

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因素	β	SE	Wald χ2	df	P	OR	95%CI
病理分化程度	1.202	0.489	6.059	1	0.014	3.328	1.278~8.671
整合素α5	2.925	0.738	15.686	1	0.000	18.626	4.381~79.191

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