腺病毒结合蛋白3在肝细胞癌中的表达与缺氧及临床预后的相关性  

Expressions of B cell lymphoma/leukemia 2/adenovirus binding protein 3 in hepatocellular carcinoma correlate with the hypoxic response and postoperative recurrence

作　　者：邱延松 辛磊[1] 王磊 周颖奇 Qiu Yansong;Xin Lei;Wang Lei;Zhou Yingqi(Department of Surgery,South Hospital of Yantai Mountain Hospital of Yantai City,Yantai 264000,China;Department of Hepatobiliary and Pancreatic Surgery,Changhai Hospital Affiliated to Naval Military Medical University,Shanghai 200433,China)

机构地区：[1]烟台市烟台山医院南院外科,264000 [2]海军军医大学附属长海医院肝胆胰外科,上海200433

出　　处：《中华实验外科杂志》2020年第7期1297-1299,共3页Chinese Journal of Experimental Surgery

基　　金：烟台市科技计划项目(2020YD051)。

摘　　要：目的探讨腺病毒结合蛋白3(BNIP-3)在肝细胞肝癌中的表达与缺氧及相关临床病理因素的关系。方法采用反转录-聚合酶链反应(RT-PCR)、荧光定量PCR和免疫组织化学方法检测烟台市烟台山医院2016年11月至2019年8月之间手术的65例肝癌组织、癌边缘组织、非癌组织中BNIP-3和缺氧诱导因子-1α(HIF-1α)的表达,分析两者表达的相关性及与相关临床病理参数的关系。不同组织中mRNA表达的差异采用t检验,蛋白表达的差异采用Kruskal-WallisH检验,BNIP-3和HIF-1α表达之间的相关性及与临床病理参数之间的比较采用Spearman相关性检验。结果肝癌组织与癌边缘组织BNIP-3、HIF-1α mRNA表达显著高于非癌组织,并且两者表达呈正相关(r=0.638、0.532,P<0.05),BNIP-3和HIF-1α在癌边缘组织蛋白表达阳性率分别73.8%、64.6%,显著高于癌组织及非癌组织(χ2=38.587、31.128,P<0.05)。相关性分析发现肝癌组织中BNIP-3蛋白表达与淋巴结转移、癌栓、TNM分期及术后复发时间有关(r=0.631、0.522、0.541、0.714,P<0.05),与性别、年龄、甲胎蛋白(AFP)、肿瘤大小、肿瘤数目、病理分期等无关;肝细胞肝癌(HCC)患者术后无瘤生存时间随癌组织BNIP-3蛋白表达阳性强度增高而延长。结论 BNIP-3在肝癌中的表达与缺氧及肝癌复发转移明显相关。Objective:The aim of the present study was to investigate the expression of B cell lymphoma/leukemia 2/adenovirus binding protein 3(BNIP-3)in hepatocellular carcinoma at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features.Methods:The expression of BNIP-3 and hypoxia inducible factor(HIF)-1αwere assessed by reverse transcriptase-polymerase chain reaction(RT-PCR),quantitative real-time PCR and immunohistochemical staining in 65 cases with human hepatocellular carcinoma,edge tissues and non-cancer tissues,then we studied the relationship between the expression and the clinic pathological feature.T test was used for mRNA expression difference,Kruskal Wallis H test was used for protein expression difference,Spearman correlation test was used for correlation between BNIP-3 and HIF-1αexpression and clinicopathological parameters.Results:Compared with the non-cancer tissues,the mRNA levels of BNIP-3 and HIF-1αin hepatocellular carcinoma tissues and tumor-surrounding tissues were much higher.BNIP-3 mRNA levels were positively correlated with HIF-1αlevels(r=0.638,0.532,P<0.05).In tumor-surrounding tissues,the positive expression rates of HIF-1αand BNIP3 proteins were 73.8%,64.6%respectively,which were higher than those in carcinoma tissues and non-cancer tissues(χ2=38.587,31.128,P<0.05).The expression of BNIP-3 in hepatocellular carcinoma(HCC)was associated with tumor thrombi,TNM classification and postoperative recurrence(r=0.631,0.522,0.541,0.714,P<0.05),but not to sex,age,alpha fetal protein(AFP)level,tumor number,tumor size,histological differentiation,the surival period without tumor was positively correlated with BNIP-3 protein expressions.Conclusion:Expressions of BNIP-3 in hepatocellular carcinoma correlate with the hypoxic response and postoperative recurrence,and can be used as an indicator for predicting the recurrence and metastasis of HCC.

关 键 词：腺病毒结合蛋白3 缺氧诱导因子1-Α 肝细胞癌 

分 类 号：R735.7[医药卫生—肿瘤]