肝细胞癌中性肽链内切酶和二肽基肽酶Ⅳ表达水平对手术切除术后患者预后的影响

摘要

Objective To investigate the implication of neutral endopeptidase (NEP) and dipeptidyl peptidase (DPP) Ⅳ in hepatocellular carcinoma tissues.Methods Cancerous tissues were obtained from 42 patients with hepatocellular carcinoma (HCC) after hepatectomy,and 42 benign liver tissues at the same time were also obtained for control in the Department of Hepatobiliary Surgery,Beijing 301st Hospital between January 2008 and July 2013.The expression of NEP and DPP Ⅳ in cancerous tissues were detected by immunohistochemical staining.Patients were checked-up every 3 months after operation.Kaplan-Meier method was used to draw the recurrence-free survival (RFS) curves and overall survival (OS) curves.Cox proportional hazards regression multivariate analysis was performed to determine the influencing factors of RFS and OS.Results NEP and DPP Ⅳ proteins were both located in the cytoplasm of hepatocellular carcinoma cells;The positive rates of NEP protein,DPP Ⅳ protein and double NEP and DPP Ⅳ protein in patients with hepatocellular carcinoma were 78.6％(33/42),71.4％(30/42) and 54.8％(23/42),respectively,all significantly higher than in normal liver tissues [2.4％ (1/42),4.8％ (2/42) and 0.0％ (0/42),P＜0.05];Multivariate analysis demonstrated that tumor differentiation,NEP expression,DPP Ⅳ expression,NEP and DPPⅣ co-expression,recurrence and metastasis of cancer were the prognostic factors of RFS and OS in patients with HCC;The survival curves showed that RFS and OS were significantly shortened and the prognosis was poorer in patients with NEP or DPP Ⅳ or both of them positive in cancerous tissues.Conclusion The expression of NEP and DPP Ⅳ might be the risk factors for the poor prognosis in patients with HCC.%目的 探讨肝癌组织中性肽链内切酶(NEP)和二肽基肽酶Ⅳ(DPPⅣ)表达水平对肝细胞癌(HCC)患者肝癌切除术后预后的影响.方法 选择2008年1月～2013年7月北京第301医院肝胆外科行肝癌切除治疗的HCC患者42例,选择同时期检查的42例肝良性肿瘤患者肝组织作为对照.采用免疫组化法检测NEP和DPPⅣ.采用Kaplan-Meier法进行无复发生存(RFS)曲线和总生存(OS)曲线绘制,采用Cox比例风险回归模型进行多因素分析,确定影响RFS和OS的因素.结果 NEP和DPPⅣ蛋白均定位于HCC细胞胞浆;HCC组织NEP蛋白阳性率为78.6％(33/42),DPPⅣ蛋白阳性率为71.4％(30/42),NEP和PPⅣ蛋白双阳性率为54.8％(23/42),均显著高于正常组织[2.4％(1/42)、4.8％(2/42)和0.0％(0/42),P＜ 0.05];经单因素和多因素分析显示,肿瘤分化、NEP表达、DPPⅣ表达、NEP和DPPⅣ共表达、复发、癌细胞远处转移是影响HCC患者RFS和OS的独立危险因素;生存曲线显示,HCC组织NEP阳性、DPPⅣ阳性和NEP/DPPⅣ均阳性表达者RFS和OS显著缩短,预后差.结论 NEP和DPPⅣ表达水平是HCC患者预后不良的危险因素.