胆管癌中转录因子EB和自噬相关蛋白Beclin 1的表达及其与预后的关系

Expression of transcription factor EB and autophagy-associated protein Beclin 1 in cholangiocarcinoma and their relationship with prognosis

目的探讨胆管癌中转录因子EB(transcription factor EB,TFEB)与自噬相关蛋白Beclin 1的表达与临床预后的相关性。方法收集广西中医药大学附属瑞康医院2011年1月~2018年1月行外科手术切除且获得随访的24例肝内胆管癌及51例肝外胆管癌的临床及病理资料。采用免疫组化EnVision两步法检测胆管癌及癌旁正常胆管上皮组织中TFEB与Beclin 1的表达,分析两者表达与胆管癌临床病理特征及预后的关系。结果与癌旁正常胆管上皮相比,TFEB在50.00%(12/24)的肝内胆管癌和47.06%(24/51)的肝外胆管癌中高表达(P均<0.05)。Beclin 1在47.06%(24/51)的肝外胆管癌中高表达(P<0.05)。TFEB和Beclin 1在肝外胆管癌中的表达呈显著负相关(P<0.05)。TFEB蛋白表达与肿瘤大小、淋巴结转移、血管侵犯及AJCC分期呈正相关(P均<0.05),Beclin 1蛋白表达与肿瘤大小、淋巴结转移、血管侵犯及AJCC分期呈负相关(P均<0.05)。肝内及肝外胆管癌TFEB高表达者的无复发生存期和总生存期显著低于低表达者(P均<0.05)。而肝内及肝外胆管癌Beclin 1高表达者的无复发生存期和总生存期显著高于低表达者(P均<0.05)。Cox多因素分析结果显示,TFEB高表达及Beclin 1低表达为影响肝内及肝外胆管细胞癌患者无复发生存期和总生存期的独立危险因素(P均<0.05)。结论胆管癌组织中TFEB及Beclin 1的表达异常提示溶酶体可能通过下调Beclin 1表达抑制肿瘤自噬,这与胆管癌的发生、发展和不良预后相关。

Purpose To study the relationship between the expression of transcription factor EB(TFEB)and autophagy-associated protein Beclin 1 in cholangiocarcinoma and clinical prognosis.Methods The clinical and pathological data of 24 cases of intrahepatic cholangiocarcinoma and 51 cases of extrahepatic cholangiocarcinoma who underwent surgical resection in our hospital from January 2011 to January 2018 were collected.The expression of TFEB and Beclin 1 in cholangiocarcinoma and adjacent normal bile duct tissue was detected by immunohistochemical method,and their relationship with clinicopathological features and prognosis of cholangiocarcinoma was analyzed.Results Compared with the normal bile duct epithelia adjacent to the cancer,TFEB was highly expressed in 50.00%(12/24)of intrahepatic cholangiocarcinoma cases and 47.06%(24/51)of extrahepatic cholangiocarcinoma cases(P<0.05).Beclin 1 was highly expressed in 47.06%(24/51)of extrahepatic cholangiocarcinoma cases(P<0.05).There was a significant negative correlation between the expression of TFEB and Beclin 1 in extrahepatic cholangiocarcinoma(P<0.05).The expression of TFEB protein was positively correlated with tumor size,lymph node metastasis,vascular invasion and AJCC stage,while the expression of Beclin 1 protein was on the contrary(P<0.05).The recurrence-free survival time and total survival time of patients with high expression of TFEB were significantly shorter than those with low expression of TFEB(P<0.05).The recurrence-free survival time and total survival time in intrahepatic and extrahepatic cholangiocarcinoma with high expression of Beclin 1 were significantly longer than those with low expression of Beclin 1(P<0.05).Cox multivariate analysis showed that high expression of TFEB and low expression of Beclin 1 were independent risk factors for recurrence-free survival and total survival in patients with intrahepatic and extrahepatic cholangiocarcinoma(P<0.05).Conclusion The abnormal expression of TFEB and Beclin 1 in cholangiocarcinoma suggests that lysosome may inhibit autophagy by down-regulating the expression of Beclin 1,which is related to the occurrence,development and poor prognosis of cholangiocarcinoma.