视黄醇结合蛋白4在三阴性乳腺癌中的表达及与上皮间质转化和临床预后的关系

Expression of RBP4 in triple-negative breast cancer and its relationship with epithelial mesenchymal transformation and clinical prognosis

目的探索视黄醇结合蛋白4(retinol binding protein 4,RBP4)在三阴性乳腺癌(triple negative breast cancer,TNBC)中的表达及与上皮间质转化(epithelial mesenchymal transition,EMT)和临床预后的关系。方法回顾性收集临沂市中心医院乳腺外科于2018年1月1日至2021年12月1日获取的160例TNBC患者的临床资料及手术标本存档蜡块,采用免疫组织化学的方法检测癌及癌旁正常组织中RBP4、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)的表达情况;分析RBP4表达与TNBC患者临床病理特性的相关性;分析RBP4表达与E-cadherin及N-cadherin表达的相关性;分析RBP4表达对TNBC患者预后的影响;评估RBP4及相关临床病理因素对TNBC患者预后的影响。结果癌组织RBP4及N-cadherin表达水平显著高于癌旁组织,癌组织E-cadherin表达水平显著低于癌旁组织;RBP4阳性TNBC患者更易出现低级别组织学分级、分期更高、脉管癌栓、淋巴结转移及Ki67阳性比例>30%(χ^(2)=9.06,9.78,9.12,8.36,37.97,P=0.003,0.001,0.002,0.004,0.000);RBP4与N-cadherin表达有明显正相关性,与E-cadherin表达有明显负相关性(r=0.423,-0.338,P=0.000,0.000);相比RBP4阴性患者,RBP4阳性TNBC患者的无进展生存期(progression free survival,PFS)更短(P=0.048),而RBP4阳性及RBP4阴性患者的总生存期(overall survival,OS)差异无统计学意义(P=0.188);肿瘤T分期、脉管侵犯、淋巴结转移、Ki67表达指数>30%、RBP4表达、E-cadherin及N-cadherin表达是影响TNBC患者复发的关键性因素,其中E-cadherin是保护性因素,其余均为危险因素。结论RBP4在TNBC中高表达,且与其恶性行为有潜在的关联,RBP4高表达患者PFS更短。

Objective To investigate the expression of RBP4 in triple negative breast cancer(TNBC)and its relationship with epithelial mesenchymal transformation(EMT)and clinical prognosis.Methods The clinical data and archival wax blocks of 160 TNBC patients obtained from the Department of Breast Surgery of Linyi Central Hospital from Jan.1,2018 to Dec.1,2021 were retrospectively collected.The expressions of retinol-binding protein(RBP4),E-cadherin and N-cadherin in cancer and adjacent normal tissues were detected by immunohistochemistry(IHC).The correlation between RBP4 expression and clinicopathological characteristics of TNBC patients was analyzed.The correlation between the expression of RBP4 and E-cadherin and N-cadherin was analyzed.Kaplan-Meier was used to analyze the effect of RBP4 expression on the prognosis of TNBC patients.Multivariate COX regression analysis was used to evaluate the effect of RBP4 and related clinicopathological factors on the prognosis of TNBC patients.Results In contrast,the expression levels of RBP4 and N-cadherin in cancer tissues were significantly higher than those in para-cancer tissues,and the expression levels of E-cadherin in cancer tissues were significantly lower than those in para-cancer tissues.Rbp4-positive TNBC patients were more likely to have low grade histological grade,T2-4 stage,vascular cancer thrombus,lymph node metastasis and Ki-67 positive ratio>30%(χ^(2)=9.06,9.78,9.12,8.36,37.97,P=0.003,0.001,0.002,0.004,0.000).RBP4 was positively correlated with N-cadherin expression and negatively correlated with E-cadherin expression(r=0.423,-0.338,P=0.000,0.000).Compared with RBP4-negative patients,RBP4-positive TNBC patients had shorter PFS(P=0.048),while there was no significant difference in OS between RBP4-positive and RBP4-negative patients(P=0.188).T stage of tumor,vascular invasion,lymph node metastasis,Ki-67 expression index>30%,RBP4 expression,E-cadherin and N-cadherin expression were the key factors affecting the recurrence of TNBC patients,of which E-cadherin was the protective factor,and the rest were risk factors.Conclusion RBP4 is highly expressed in cancer tissues and is potentially associated with malignant behavior of TNBC.Patients with high expression of RBP4 are more likely to have shorter PFS.