Article(id=1324050786799460686, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202511204, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1763049600000, receivedDateStr=2025-11-14, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793607907246, onlineDateStr=2026-11-02, pubDate=1778342400000, pubDateStr=2026-05-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793607907246, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793607907246, creator=13701087609, updateTime=1793607907246, updator=13701087609, issue=Issue{id=1324050669933572771, tenantId=1146029695717560320, journalId=1227665162245664772, year='2026', volume='53', issue='9', pageStart='1537', pageEnd='1728', issueExtLink='null', onlineDate='null', pubDate='1778342400000', pubDateStr='2026-05-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1793607879384, creator='13701087609', updateTime=1793670100562, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1324311644528050975, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1324311644528050976, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1324050669933572771, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=1684, endPage=1690, ext={EN=ArticleExt(id=1324050788296827215, articleId=1324050786799460686, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Relationship between cytoplasmic poly(A)-binding protein 1 expression and chemotherapy prognosis in triple-negative breast cancer, columnId=1228016572065837304, journalTitle=Modern Preventive Medicine, columnName=Experimental Technology and Applications, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the prognostic value of cytoplasmic poly (A)-binding protein 1 (PABPC1) expression, alone and in combination with Ki-67 and P53, in evaluating chemotherapy prognosis in patients with triple-negative breast cancer (TNBC).

Methods

A retrospective analysis was conducted on the clinicopathological data of 155 patients diagnosed with and treated for TNBC at the Affiliated Hospital of Southwest Medical University between January 2014 and December 2021. Immunohistochemistry was employed to detect the expression levels of PABPC1, Ki-67, and P53 in tumor tissues. Their correlations with patient overall survival (OS) and disease-free survival (DFS) were subsequently analyzed.

Results

Among the 155 patients included in the study, high PABPC1 expression was observed in 59 cases (38.1%), Ki-67 positivity in 119 cases (76.8%), and P53 positivity in 70 cases (45.2%). PABPC1 expression, patient age, and pathological stage significantly influenced the postoperative survival of TNBC patients. In contrast, tumor location, clinical stage, lymph node metastasis, HER-2 expression, Ki-67 expression, and P53 expression were not significantly associated with survival. In the patient subgroup with high PABPC1 expression, those who received postoperative chemotherapy demonstrated improved OS compared to those who did not, although this difference did not reach statistical significance. However, within the subgroup of patients exhibiting both high PABPC1 expression and Ki-67 positivity, those who received postoperative chemotherapy had a significantly longer OS compared to their counterparts who did not undergo chemotherapy.

Conclusion

TNBC patients with low PABPC1 expression exhibit favorable survival outcomes, irrespective of whether they receive chemotherapy. Conversely, patients with high PABPC1 expression have a poorer prognosis. The combined assessment of PABPC1 and Ki-67 holds clinical significance, as patients displaying both high PABPC1 expression and Ki-67 positivity may derive substantial benefit from postoperative adjuvant chemotherapy.

, authors=Xia GUAN1, Ai-chun LONG2, Cui-wei ZHANG2, 3, Jun LIU2, Xue WEN2, Wen-bo LONG2, 3, authorsList=Xia GUAN, Ai-chun LONG, Cui-wei ZHANG, Jun LIU, Xue WEN, Wen-bo LONG, authorCompany=null, correspAuthors=Wen-bo LONG, authorNote=null, correspAuthorsNote=null, 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, fund=null), CN=ArticleExt(id=1324050789802582362, articleId=1324050786799460686, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=细胞质多聚(A)结合蛋白1表达与三阴乳腺癌化疗预后的关系, columnId=1228016572288135432, journalTitle=现代预防医学, columnName=实验技术及其应用, runingTitle=null, highlight=null, articleAbstract=
目的

研究细胞质多聚腺苷酸结合蛋白1[poly(A)binding protein cytoplasmic 1,PABPC1]单独及联合Ki-67、P53表达对三阴性乳腺癌(triple-negative breast cancer,TNBC)患者化疗预后的评估价值。

方法

回顾性分析了2014年1月—2021年12月,在西南医科大学附属医院确诊并接受治疗的155例TNBC患者的临床病理资料。采用免疫组织化学法检测肿瘤组织中PABPC1、Ki-67及P53的表达水平,并分析其与患者总生存期和无病生存期的相关性。

结果

在155例患者中,PABPC1高表达59例(38.1%),Ki-67阳性119例(76.8%),P53阳性70例(45.2%)。PABPC1表达、患者年龄和病理分期对TNBC患者术后生存有显著影响,而肿瘤位置、临床分期、淋巴结转移、HER-2表达、Ki-67表达和P53表达与患者生存未见显著相关。在PABPC1高表达组中,相比未接受术后化疗者,接受术后化疗的患者总生存期有所改善但是没有达到显著水平。然而,在PABPC1高表达且Ki-67阳性的患者中,接受术后化疗者的总生存期较未化疗者显著延长。

结论

PABPC1低表达的TNBC患者无论是否接受化疗,均表现出良好的生存结局;而PABPC1高表达者预后较差。联合检测PABPC1与Ki-67具有临床意义,其中PABPC1高表达且Ki-67阳性的患者可能从术后辅助化疗中显著获益。

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关霞(1979—),女,本科,主治医师,研究方向:乳腺癌浸润与转移

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龙文波,E-mail:
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Cureus, 2021, 13(7): e16788., articleTitle=Ki-67 and its relation with complete pathological response in patients with breast cancer, refAbstract=null), Reference(id=1324050797327163832, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, doi=null, pmid=null, pmcid=null, year=2018, volume=172, issue=2, pageStart=437, pageEnd=444, url=null, language=null, rfNumber=[23], rfOrder=27, authorNames=Bae SY, Nam SJ, Jung Y, journalName=Breast Cancer Research and Treatment, refType=null, unstructuredReference=Bae SY, Nam SJ, Jung Y, et al. Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer [J]. Breast Cancer Research and Treatment, 2018, 172(2): 437-444., articleTitle=Differences in prognosis and efficacy of chemotherapy by p53 expression in triple-negative breast cancer, refAbstract=null)], funds=[Fund(id=1324050794839941531, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, awardId=2021-JYJ-65, language=CN, fundingSource=泸州市科技计划项目(2021-JYJ-65), fundOrder=null, country=null), Fund(id=1324050794902856092, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, awardId=2024LZXNYDJ077; 2024LZXNYDJ036, language=CN, fundingSource=泸州市人民政府-西南医科大学科技战略合作项目(2024LZXNYDJ077; 2024LZXNYDJ036), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1324050790091989339, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, xref=1., ext=[AuthorCompanyExt(id=1324050790100377948, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, companyId=1324050790091989339, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Pathology, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan 610041, China), AuthorCompanyExt(id=1324050790112960861, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, companyId=1324050790091989339, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.四川省妇幼保健院 病理科,四川 成都 610041)]), AuthorCompany(id=1324050790247178590, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, xref=2., ext=[AuthorCompanyExt(id=1324050790255567199, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, companyId=1324050790247178590, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.西南医科大学附属医院 病理科,四川 泸州 646000)]), AuthorCompany(id=1324050790381396320, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, xref=3., ext=[AuthorCompanyExt(id=1324050790389784929, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, companyId=1324050790381396320, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.重大疾病精准病理诊断泸州市重点实验室,四川 泸州 646000)])], figs=[ArticleFig(id=1324050793262883213, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Figure 1, caption=ROC curve of PABPC1 expression, figureFileSmall=j7/0XS0OuzGWltU6ULvPlA==, figureFileBig=H3ZbobePXp0I8fXLEjmJ6A==, tableContent=null), ArticleFig(id=1324050793380323726, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=图1, caption=PABPC1表达的ROC

注:采用ROC分析确定PABPC1表达的最佳临界值,结果显示其位于22.5%~26.5%之间,平均值约为25%;因此,本研究将25%设定为三阴性乳腺癌PABPC1高表达与低表达的判定阈值。

, figureFileSmall=j7/0XS0OuzGWltU6ULvPlA==, figureFileBig=H3ZbobePXp0I8fXLEjmJ6A==, tableContent=null), ArticleFig(id=1324050793627787663, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Figure 2, caption=Expression of PABPC1, P53 and Ki-67 in triple negative breast cancer tissue samples (immunohistochemical DAB staining,×100), figureFileSmall=UBtU1dJA6PO9hfDo0HZHLA==, figureFileBig=YiuyqHT7NQQGFdLPmadaNg==, tableContent=null), ArticleFig(id=1324050793799754128, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=图2, caption=PABPC1、P53和Ki-67在三阴乳腺癌组织样本的表达(免疫组化DAB染色,×100)

注:图A为典型的PABPC1高表达组织样本,箭头示细胞质定位;图B为样本具有P53阴性表达;图C为Ki-67阴性表达;图D为典型的PABPC1低表达组织样本;图E为该样本P53阳性表达;图F为Ki-67阳性表达,箭头示核定位。

, figureFileSmall=UBtU1dJA6PO9hfDo0HZHLA==, figureFileBig=YiuyqHT7NQQGFdLPmadaNg==, tableContent=null), ArticleFig(id=1324050793887834513, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Figure 3, caption=Kaplan-Meier survival curve analysis of clinicopathological characteristics of TNBC patients, figureFileSmall=a3kpoUbKMeGJZmnvdiDEIA==, figureFileBig=MFVVGrrMMvDdA8ANVp61QA==, tableContent=null), ArticleFig(id=1324050793959137682, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=图3, caption=TNBC患者临床病理特征的Kaplan-Meier生存曲线分析

注:年龄<55岁及病理分期为Ⅰ/Ⅱ期的患者,其总生存期与无病生存期均显著延长;肿瘤T分期(图C、G)与淋巴结转移情况(图D、H)也显著影响患者的无病生存期;然而,肿瘤侧别(左/右)(图B、F)、HER2表达状态(图J、N)、Ki-67表达水平(图K、O)以及P53表达状态(图L、P)对总生存期和无病生存期均无显著影响。

, figureFileSmall=a3kpoUbKMeGJZmnvdiDEIA==, figureFileBig=MFVVGrrMMvDdA8ANVp61QA==, tableContent=null), ArticleFig(id=1324050794055606675, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Figure 4, caption=Kaplan-Meier survival curve analysis of the correlation between PABPC1 expression and TNBC patients who receiving chemotherapy, figureFileSmall=W1lxgY181skfHKmkxOwgdg==, figureFileBig=Qd+kWrTJz+ZUs+IYk/86rA==, tableContent=null), ArticleFig(id=1324050794231767444, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=图4, caption=PABPC1表达与TNBC患者化疗相关性的Kaplan-Meier生存曲线分析

注:PABPC1高表达患者相比低表达,具有显著减少的总生存期(图A)和无病生存期(图D);总体上看,化疗对TNBC患者的总生存期(图B)和无病生存期(图E)都没有改善;但是,无论是否接受化疗,PABPC1低表达的TNBC患者都有良好的总生存期(图C)和无病生存期(图F);接受化疗的PABPC1高表达TNBC患者的总生存期比未接受化疗的有所改善,但差异没有达到统计学意义。

, figureFileSmall=W1lxgY181skfHKmkxOwgdg==, figureFileBig=Qd+kWrTJz+ZUs+IYk/86rA==, tableContent=null), ArticleFig(id=1324050794294682005, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Figure 5, caption=Kaplan-Meier survival curve analysis of the prognostic value of combined PABPC1, Ki-67, and P53 expression for chemotherapy in TNBC patients, figureFileSmall=PJOSFl/9AYut9eU+8fb6/w==, figureFileBig=nh8GQUmTCbutB0OxOC/CLA==, tableContent=null), ArticleFig(id=1324050794361790870, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=图5, caption=PABPC1联合Ki-67和P53表达对TNBC患者化疗预后的Kaplan-Meier生存曲线分析

注:在PABPC1低表达患者中,无论是联合Ki-67或P53或同时联合两者,均表现出良好的总生存期与无病生存期;在PABPC1高表达且Ki-67阳性的患者中,接受化疗者的总生存期(图A)和无病生存期(图D)均显著长于未接受化疗者;相比之下,在PABPC1高表达且P53阳性,或PABPC1高表达且Ki-67/P53双阳性的患者中,化疗组与未化疗组的总生存期(图B、C)和无病生存期(图E、F)均未观察到显著差异。

, figureFileSmall=PJOSFl/9AYut9eU+8fb6/w==, figureFileBig=nh8GQUmTCbutB0OxOC/CLA==, tableContent=null), ArticleFig(id=1324050794441482647, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Table 1, caption=

Clinicopathological characteristics of patients and correlation analysis between PABPC1 and clinicopathological factors [n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量PABPC1低表达
(n=96)
PABPC1高表达
(n=59)
P 值
年龄(岁)0.055
<5570 (72.9)34 (57.6)
≥ 5526 (27.1)25 (42.4)
病理类型0.785
非特殊86 (89.6)54 (91.5)
其它10 (10.4)5 (8.5)
肿瘤位置0.243
左60 (62.5)31 (52.5)
右36 (37.5)28 (47.5)
肿瘤大小0.392
T1-289 (92.7)52 (88.1)
T3-47 (7.3)7 (11.9)
淋巴结转移0.177
无63 (65.6)32 (54.2)
有33 (34.4)27 (45.8)
病理分期0.215
I- II69 (71.9)36 (61.0)
III- IV27 (28.1)23 (39.0)
HER20.307
无表达40 (41.7)19 (32.2)
有表达56 (58.3)40 (67.8)
Ki-670.330
阴性25 (26.0)11 (18.6)
阳性71 (74.0)48 (81.4)
P530.248
阴性49 (51.0)36 (61.0)
阳性47 (49.0)23 (39.0)
术后治疗0.155
无26 (27.1)23 (39.0)
有70 (72.9)36 (61.0)
), ArticleFig(id=1324050794516980120, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=表1, caption=

患者的临床病理特征及PABPC1与临床病理因素的相关性分析[n(%)]

, figureFileSmall=null, figureFileBig=null, tableContent=
变量PABPC1低表达
(n=96)
PABPC1高表达
(n=59)
P 值
年龄(岁)0.055
<5570 (72.9)34 (57.6)
≥ 5526 (27.1)25 (42.4)
病理类型0.785
非特殊86 (89.6)54 (91.5)
其它10 (10.4)5 (8.5)
肿瘤位置0.243
左60 (62.5)31 (52.5)
右36 (37.5)28 (47.5)
肿瘤大小0.392
T1-289 (92.7)52 (88.1)
T3-47 (7.3)7 (11.9)
淋巴结转移0.177
无63 (65.6)32 (54.2)
有33 (34.4)27 (45.8)
病理分期0.215
I- II69 (71.9)36 (61.0)
III- IV27 (28.1)23 (39.0)
HER20.307
无表达40 (41.7)19 (32.2)
有表达56 (58.3)40 (67.8)
Ki-670.330
阴性25 (26.0)11 (18.6)
阳性71 (74.0)48 (81.4)
P530.248
阴性49 (51.0)36 (61.0)
阳性47 (49.0)23 (39.0)
术后治疗0.155
无26 (27.1)23 (39.0)
有70 (72.9)36 (61.0)
), ArticleFig(id=1324050794600866201, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=EN, label=Table 2, caption=

Multivariable Cox regression analysis of overall survival and disease-free survival of triple negative breast cancer patients

, figureFileSmall=null, figureFileBig=null, tableContent=
因素总生存期无病生存期
OR (95% CI)P 值OR (95% CI)P值
年龄(岁,参照组:<55)2.640 (1.220-5.710)0.014*1.799 (0.705-4.591)0.219
肿瘤位置(参照组:左)0.777 (0.362-1.671)0.5190.247 (0.087-0.702)0.009**
肿瘤大小(参照组:T1-2)1.710 (0.602-4.859)0.3142.493 (0.833-7.457)0.102
淋巴结转移(参照组:无)0.765 (0.298-1.959)0.5762.070 (0.638-6.714)0.226
病理分期(参照组:I- II)3.321 (1.336-8.259)0.010*1.457 (0.443-4.788)0.536
HER2(参照组:阴性)0.696 (0.311-1.557)0.3780.741 (0.271-2.030)0.560
Ki-67(参照组:阴性)0.955 (0.332-2.749)0.9321.014 (0.272-3.773)0.984
P53(参照组:阴性)2.995 (1.365-6.574)0.006**2.224 (0.845-5.855)0.105
术后治疗(参照组:无治疗)0.487 (0.226-1.050)0.0670.428 (0.169-1.088)0.075
PABPC1(参照组:低表达)3.126 (1.406-6.952)0.005**4.546 (1.729-11.923)0.002**
), ArticleFig(id=1324050794693140890, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1324050786799460686, language=CN, label=表2, caption=

三阴乳腺癌患者总生存期和无病生存期的多变量Cox回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
因素总生存期无病生存期
OR (95% CI)P 值OR (95% CI)P值
年龄(岁,参照组:<55)2.640 (1.220-5.710)0.014*1.799 (0.705-4.591)0.219
肿瘤位置(参照组:左)0.777 (0.362-1.671)0.5190.247 (0.087-0.702)0.009**
肿瘤大小(参照组:T1-2)1.710 (0.602-4.859)0.3142.493 (0.833-7.457)0.102
淋巴结转移(参照组:无)0.765 (0.298-1.959)0.5762.070 (0.638-6.714)0.226
病理分期(参照组:I- II)3.321 (1.336-8.259)0.010*1.457 (0.443-4.788)0.536
HER2(参照组:阴性)0.696 (0.311-1.557)0.3780.741 (0.271-2.030)0.560
Ki-67(参照组:阴性)0.955 (0.332-2.749)0.9321.014 (0.272-3.773)0.984
P53(参照组:阴性)2.995 (1.365-6.574)0.006**2.224 (0.845-5.855)0.105
术后治疗(参照组:无治疗)0.487 (0.226-1.050)0.0670.428 (0.169-1.088)0.075
PABPC1(参照组:低表达)3.126 (1.406-6.952)0.005**4.546 (1.729-11.923)0.002**
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细胞质多聚(A)结合蛋白1表达与三阴乳腺癌化疗预后的关系
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关霞 1 , 龙爱纯 2 , 张翠薇 2, 3 , 刘俊 2 , 文雪 2 , 龙文波 2, 3
现代预防医学 | 实验技术及其应用 2026,53(9): 1684-1690
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现代预防医学 |实验技术及其应用 2026 , 53 (9) : 1684 -1690
细胞质多聚(A)结合蛋白1表达与三阴乳腺癌化疗预后的关系
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关霞1, 龙爱纯2, 张翠薇2, 3, 刘俊2, 文雪2, 龙文波2, 3
作者信息
  • 1.四川省妇幼保健院 病理科,四川 成都 610041
  • 2.西南医科大学附属医院 病理科,四川 泸州 646000
  • 3.重大疾病精准病理诊断泸州市重点实验室,四川 泸州 646000
通讯作者:
龙文波,E-mail:
作者简介:

关霞(1979—),女,本科,主治医师,研究方向:乳腺癌浸润与转移

Relationship between cytoplasmic poly(A)-binding protein 1 expression and chemotherapy prognosis in triple-negative breast cancer
Xia GUAN1, Ai-chun LONG2, Cui-wei ZHANG2, 3, Jun LIU2, Xue WEN2, Wen-bo LONG2, 3
Affiliations
  • Department of Pathology, Sichuan Provincial Maternity and Child Health Care Hospital, Chengdu, Sichuan 610041, China
出版时间: 2026-05-10 doi: 10.20043/j.cnki.MPM.202511204
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目的

研究细胞质多聚腺苷酸结合蛋白1[poly(A)binding protein cytoplasmic 1,PABPC1]单独及联合Ki-67、P53表达对三阴性乳腺癌(triple-negative breast cancer,TNBC)患者化疗预后的评估价值。

方法

回顾性分析了2014年1月—2021年12月,在西南医科大学附属医院确诊并接受治疗的155例TNBC患者的临床病理资料。采用免疫组织化学法检测肿瘤组织中PABPC1、Ki-67及P53的表达水平,并分析其与患者总生存期和无病生存期的相关性。

结果

在155例患者中,PABPC1高表达59例(38.1%),Ki-67阳性119例(76.8%),P53阳性70例(45.2%)。PABPC1表达、患者年龄和病理分期对TNBC患者术后生存有显著影响,而肿瘤位置、临床分期、淋巴结转移、HER-2表达、Ki-67表达和P53表达与患者生存未见显著相关。在PABPC1高表达组中,相比未接受术后化疗者,接受术后化疗的患者总生存期有所改善但是没有达到显著水平。然而,在PABPC1高表达且Ki-67阳性的患者中,接受术后化疗者的总生存期较未化疗者显著延长。

结论

PABPC1低表达的TNBC患者无论是否接受化疗,均表现出良好的生存结局;而PABPC1高表达者预后较差。联合检测PABPC1与Ki-67具有临床意义,其中PABPC1高表达且Ki-67阳性的患者可能从术后辅助化疗中显著获益。

三阴乳腺癌  /  胞质多聚(A)结合蛋白1  /  化疗预后  /  Ki-67  /  P53
Objective

To investigate the prognostic value of cytoplasmic poly (A)-binding protein 1 (PABPC1) expression, alone and in combination with Ki-67 and P53, in evaluating chemotherapy prognosis in patients with triple-negative breast cancer (TNBC).

Methods

A retrospective analysis was conducted on the clinicopathological data of 155 patients diagnosed with and treated for TNBC at the Affiliated Hospital of Southwest Medical University between January 2014 and December 2021. Immunohistochemistry was employed to detect the expression levels of PABPC1, Ki-67, and P53 in tumor tissues. Their correlations with patient overall survival (OS) and disease-free survival (DFS) were subsequently analyzed.

Results

Among the 155 patients included in the study, high PABPC1 expression was observed in 59 cases (38.1%), Ki-67 positivity in 119 cases (76.8%), and P53 positivity in 70 cases (45.2%). PABPC1 expression, patient age, and pathological stage significantly influenced the postoperative survival of TNBC patients. In contrast, tumor location, clinical stage, lymph node metastasis, HER-2 expression, Ki-67 expression, and P53 expression were not significantly associated with survival. In the patient subgroup with high PABPC1 expression, those who received postoperative chemotherapy demonstrated improved OS compared to those who did not, although this difference did not reach statistical significance. However, within the subgroup of patients exhibiting both high PABPC1 expression and Ki-67 positivity, those who received postoperative chemotherapy had a significantly longer OS compared to their counterparts who did not undergo chemotherapy.

Conclusion

TNBC patients with low PABPC1 expression exhibit favorable survival outcomes, irrespective of whether they receive chemotherapy. Conversely, patients with high PABPC1 expression have a poorer prognosis. The combined assessment of PABPC1 and Ki-67 holds clinical significance, as patients displaying both high PABPC1 expression and Ki-67 positivity may derive substantial benefit from postoperative adjuvant chemotherapy.

Triple negative breast cancer  /  Cytoplasmic poly(A)-binding protein 1  /  Chemotherapy prognosis  /  Ki-67  /  P53
关霞, 龙爱纯, 张翠薇, 刘俊, 文雪, 龙文波. 细胞质多聚(A)结合蛋白1表达与三阴乳腺癌化疗预后的关系. 现代预防医学, 2026 , 53 (9) : 1684 -1690 . DOI: 10.20043/j.cnki.MPM.202511204
Xia GUAN, Ai-chun LONG, Cui-wei ZHANG, Jun LIU, Xue WEN, Wen-bo LONG. Relationship between cytoplasmic poly(A)-binding protein 1 expression and chemotherapy prognosis in triple-negative breast cancer[J]. Modern Preventive Medicine, 2026 , 53 (9) : 1684 -1690 . DOI: 10.20043/j.cnki.MPM.202511204
三阴乳腺癌(triple negative breast cancer, TNBC)是指在病理检测中雌激素受体、孕激素受体、人表皮生长因子受体-2表达均为阴性的乳腺癌亚型[1]。TNBC具有异质性高、易发生转移与复发的特点,且对内分泌治疗和HER-2靶向治疗均不敏感[2]。TNBC并非单一疾病实体,而是一组在临床表现、组织病理及分子特征上存在显著差异的肿瘤集合。TNBC可以被分为六种亚型,包括基底样亚型1和2、免疫调节亚型、间叶细胞亚型、间叶干细胞亚型和腔内雄激素受体亚型[3]。Burstein等人[4]则把TNBC划分为四种亚型:雄激素受体阳性亚型、间叶细胞亚型、基底样免疫抑制亚型和基底样免疫激活亚型。
目前,化疗仍是TNBC系统治疗的基石[1-2,5]。无论是作为新辅助治疗还是辅助治疗,标准化疗方案均能为患者带来明确的生存获益[6]。然而,受肿瘤异质性及化疗耐药等因素影响,仍有相当一部分患者预后不良。
细胞质多聚(A)结合蛋白1[poly(A)binding protein cycloplast 1, PABPC1]是一种在细胞质mRNA定位、稳定性维持及翻译过程中发挥关键调控作用的RNA结合蛋白[7]。研究表明,PABPC1表达失调与肝癌、卵巢癌、食管鳞状细胞癌及鼻咽癌等多种恶性肿瘤的进展密切相关[8]。本课题组前期工作初步探讨了PABPC1在乳腺癌中的预后价值,发现其对Luminal B型及HER2阳性型乳腺癌具有一定预后意义[9]。然而,该研究受限于样本量较小(经倾向评分匹配后仅纳入83例),且主要聚焦于激素受体阳性与HER2阳性亚型间的差异,未能阐明PABPC1在TNBC这一高危亚型中与化疗预后的关联。此外,PABPC1与乳腺癌中关键增殖标志物Ki-67及抑癌因子P53之间的相关性亦有待揭示。因此,本研究通过扩大样本量,聚焦TNBC患者群体,系统评估PABPC1的表达水平及其与Ki-67、P53的相关性,旨在明确PABPC1在TNBC化疗预后预测中的潜在价值。
本研究回顾性纳入2014年1月—2021年12月在西南医科大学附属医院经病理确诊的155例TNBC患者。所有患者均为女性,年龄范围为29~89岁,平均年龄(52.8±10.0)岁;肿瘤最大径为0.4~9.0 cm,平均(2.8±1.5)cm;淋巴结转移数目为0~21个,平均(1.7±3.6)个。纳入标准:(1)经病理学确诊为原发性乳腺癌;(2)接受乳房切除术或保乳手术;(3)手术切缘阴性;(4)无其他严重合并疾病;(5)具备完整随访资料。所有患者或其家属均签署知情同意书,本研究经西南医科大学附属医院伦理委员会批准(批件号:KY2025105)。术后辅助化疗方案主要包括多西他赛+多柔比星+环磷酰胺或多西他赛+铂类方案。
采用免疫组织化学法检测ER和PR表达,结合免疫组织化学与原位杂交(fluorescence in situ hybridization,FISH)法检测HER-2表达。肿瘤细胞核内激素受体标记阳性细胞<1%视为PR、ER 阴性,HER-2表达为0、1+、2+且FISH-判定为HER-2阴性[10]。PR、ER和HER-2同时为阴性者确诊为TNBC。
本研究所有免疫组织化学检测(PABPC1、P53、Ki-67)均采用西南医科大学附属医院病理科保存的石蜡包埋组织样本,检测时间为2024年6月—2025年6月。实验操作参照课题组既往已发表的方法进行[8-9]。采用数字化病理切片扫描仪(宁波江丰生物信息技术有限公司,型号KF-PRO-020)对整张组织切片进行扫描,并通过计算阳性染色肿瘤细胞占全部肿瘤细胞的百分比,定量评估各蛋白的表达水平。每例样本的蛋白表达数据均为三次独立免疫组化检测结果的平均值。Ki-67与P53的阳性判定阈值参照已有文献设定,分别为≥30%和≥10%[11-12]。PABPC1的高表达的临界值通过受试者工作特征曲线(receiver operat characteristic,ROC)确定[9],其最佳截断值约为25%。据此将PABPC1高表达定义为阳性细胞比例≥25.0%,低表达定义为<25.0%。见图1。
患者于术后接受定期随访,间隔为3~6个月。随访起点为手术当日。研究终点包括总生存期和无病生存期。总生存期定义为手术日期至随访截止或任何原因导致死亡的时间;无病生存期定义为手术日期至随访截止、局部复发或远处转移发生的时间。本研究最早病例入组时间为2014年1月,末次随访时间为2024年12月。
采用IBM SPSS 22.0版软件进行数据分析。分类变量(如临床病理特征及亚型分布)的比较采用Fisher精确检验(双侧)。生存分析采用Kaplan-Meier法绘制生存曲线,组间差异比较采用Log-rank检验。采用Cox比例风险回归模型进行多因素预后分析。检验水准α=0.05。
通过ROC曲线确立PABPC1高表达临界值,见图1,并分析其免疫组化表达特征,见图2。结果,155例TNBC患者中,119例(76.8%)检测到PABPC1表达,其中高表达59例(38.1%);154例(99.4%)检测到Ki-67表达,其中阳性表达119例(76.8%);83例(53.5%)检测到P53表达,其中阳性表达70例(45.2%)。PABPC1高表达组与低表达组在年龄、肿瘤分期、HER2表达等临床病理因素上的差异均无统计学意义。见表1。
155例患者中,死亡30例(19.4%),复发/转移22例(14.2%)。单因素生存分析显示,年龄≥55岁、病理分期较晚与总生存期和无病生存期的缩短显著相关,T分期和淋巴结转移与无病生存期显著相关,而肿瘤位置、HER-2表达、Ki-67表达和P53表达对患者术后生存无显著影响。见图3。
PABPC1高表达组患者的总生存期和无病生存期显著低于低表达组,见图4 A和D。155例患者中,106例(68.4%)接受了术后辅助化疗,但接受化疗与未接受化疗患者的总体生存期与无病生存期均无统计学差异,见图4 B和E。根据PABPC1表达水平进行分层分析发现,无论是否接受术后化疗,PABPC1低表达组的总生存期和无病生存期均显著优于高表达组,见图4 C和F。在PABPC1高表达组中,接受术后化疗者的无病生存期较未化疗者显著延长,总生存期有改善趋势但差异未达到统计学意义(P=0.104)。
在155例患者中,Ki-67与P53均呈现较高阳性率。将PABPC1分别与Ki-67及P53进行联合分析发现:PABPC1联合Ki-67可更好区分接受术后化疗患者的生存结局;而PABPC1联合P53,或三者联合,其预后判断能力较单独使用PABPC1未见显著提高,见图5。进一步亚组分析表明,术后化疗可显著改善PABPC1高表达以及Ki-67阳性患者的总生存期和无病生存期;而在不满足该表达特征的患者中,术后化疗未带来显著生存获益。
Cox比例风险回归模型多因素分析结果显示,年龄较高、病理分期较晚及P53阳性是患者死亡风险的独立危险因素;肿瘤位于右乳相较于左乳,复发转移风险显著降低,见表2。此外,PABPC1高表达患者相较于低表达者具有更高的死亡风险与复发转移风险,差异具有统计学意义。
TNBC作为乳腺癌中异质性最强的亚型之一,具有预后差、复发风险高等临床特点。其分子生物学特征复杂,目前与预后相关的机制尚未完全明确。既往基于转录组数据提出的分型方案虽有助于区分TNBC内部亚型,但多来源于西方人群[4,13],或依赖于成本较高、临床推广受限的技术平台[14]。因此,建立一种经济、高效且适用于广泛临床场景的TNBC分型策略,仍是当前亟待解决的重要问题。本研究结果表明,PABPC1表达水平可作为TNBC分型策略。依据PABPC1表达水平,可将TNBC患者分为PABPC1低表达与高表达两种亚型。无论是否接受化疗,PABPC1低表达亚型患者均表现良好的生存结局,而高表达亚型患者预后显著不良。进一步分析显示,PABPC1联合Ki-67对TNBC预后的预测效能优于单独使用PABPC1。这提示,PABPC1可能为TNBC的预后评估及个体化治疗决策提供新的参考依据。
P53与Ki-67免疫组化检测是乳腺癌病理评估中广泛应用的指标。P53作为重要的抑癌基因,其蛋白表达异常与肿瘤发生发展密切相关。在TNBC中TP53基因突变频率较高,因此P53蛋白免疫组化阳性率也相应升高[15],且其表达与TNM分期、淋巴结转移等临床病理特征相关[16]。本研究患者P53阳性细胞百分比平均为29.7%,与既往报道一致。多因素分析显示P53表达与患者生存显著相关,该结果与部分文献相符[17]。然而在Kaplan-Meier生存分析中,P53阳性与阴性患者的总体生存期及无病生存期未见显著差异,可能与本研究样本量相对有限有关。于P53不同,Ki-67是反映细胞增殖活性的核蛋白,其高表达常提示肿瘤增殖活跃。TNBC中Ki-67普遍高表达,亦是其侵袭性较强的生物学特征之一[18]。本组病例Ki-67阳性率接近100%,符合文献报道。尽管Ki-67高表达通常被认为与不良预后相关,但也有研究未发现其与生存存在独立关联[19],本研究亦未显示Ki-67表达与生存时间存在统计学相关性。值得注意的是,TNBC中Ki-67阳性判读阈值目前尚无统一标准,文献报道的临界值介于10%~50%以上不等[20],其设定常受研究人群、检测方法及终点指标等多种因素影响。本研究采用30%作为阈值,主要依据Zhu等[11]基于大样本TNBC队列(n=1 800)确立的标准,具有较好的参考价值。然而,该阈值是否为联合PABPC1评估预后的最佳截断值,仍有待后续研究进一步验证。
目前,化疗仍是多数TNBC患者的标准治疗方式。然而,化疗药物的细胞毒性及患者个体差异等因素制约其疗效,仅部分TNBC患者可以从化疗中明确获益[21]。因此,借助分子生物学标志物对TNBC进行亚群划分,以识别潜在化疗敏感人群,具有重要临床意义。本研究探讨了PABPC1表达与化疗反应之间的关系。结果显示,在PABPC1低表达患者中,化疗并未带来显著生存改善:接受与未接受化疗患者的五年总生存率分别为92.3%和90.8%,无病生存率分别为90.1%和92.3%,差异均无统计学意义。这提示PABPC1低表达可能代表一类不易从辅助化疗中获益的TNBC亚群。Ki-67和P53是已知与化疗相关的标志物:前者常被用于评估乳腺癌化疗敏感性[22],后者阳性表达则被部分研究报道与TNBC化疗敏感性提升相关[23]。本研究进一步将PABPC1分别与Ki-67及P53进行联合分析,发现仅在PABPC1高表达且Ki-67阳性患者中,辅助化疗可显著延长术后生存时间;而在PABPC1高表达且P53阳性,或PABPC1高表达且Ki-67/P53双阳性患者中,化疗并未带来显著生存获益。因此,PABPC1高表达联合Ki-67阳性或可作为识别辅助化疗获益人群的分子分型依据,为临床化疗决策提供新线索。
综上所述,本研究表明PABPC1表达水平是TNBC患者总生存期和无病生存期的独立预后分子标志物:PABPC1低表达患者预后良好,而PABPC1高表达患者预后显著不良。在治疗反应方面,PABPC1低表达患者未能从辅助化疗中获得显著生存获益;而在PABPC1高表达患者中,尽管整体化疗未显著改善总生存期,但在同时伴有Ki-67阳性的亚组中,化疗可显著延长其总生存期。值得指出的是,本研究基于TNBC队列通过ROC曲线确定的PABPC1高/低表达阈值为25%,高于本课题组既往在涵盖各亚型乳腺癌的混合队列中所报道的20%[9]。这一差异提示,不同乳腺癌亚型的PABPC1表达阈值可能并不相同,因此针对特定亚型(如TNBC)独立确定其临界值具有必要性,而其他亚型的最佳阈值仍有待进一步研究。此外,受限于样本量,该阈值在更广泛人群中的稳定性及其影响因素,尚需在未来大样本研究中予以验证。
  • 泸州市科技计划项目(2021-JYJ-65)
  • 泸州市人民政府-西南医科大学科技战略合作项目(2024LZXNYDJ077; 2024LZXNYDJ036)
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2026年第53卷第9期
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doi: 10.20043/j.cnki.MPM.202511204
  • 接收时间:2025-11-14
  • 首发时间:2026-11-02
  • 出版时间:2026-05-10
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  • 收稿日期:2025-11-14
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泸州市科技计划项目(2021-JYJ-65)
泸州市人民政府-西南医科大学科技战略合作项目(2024LZXNYDJ077; 2024LZXNYDJ036)
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    1.四川省妇幼保健院 病理科,四川 成都 610041
    2.西南医科大学附属医院 病理科,四川 泸州 646000
    3.重大疾病精准病理诊断泸州市重点实验室,四川 泸州 646000

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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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