胆管癌miR-551b表达变化的临床意义及其靶基因生物信息学分析

Clinical significance of miR-551b expression in cholangiocarcinoma and bioinformatics analysis of its target gene

目的研究胆管癌miR-551b表达变化的临床意义,并采用生物信息学方法分析其靶基因。方法选择2014-10至2018-10在武警安徽总队医院行胆管癌根治术的78例患者作为胆管癌组,并选择同期因胆管结石行Roux-en-Y胆肠吻合术的40例患者作为对照组,检测胆管癌组织和正常胆管组织中miR-551及细胞周期素D1(cyclinD1)的表达量,随访胆管癌患者的总生存期(OS)。结果胆管癌组织中miR-551b的表达量低于正常胆管组织且术前血清CA19-9升高、术前血清CEA升高、TNMⅢ期、低未分化、微血管侵犯患者胆囊癌组织中miR-551b的表达量明显低于术前血清CA19-9正常、术前血清CEA正常,TNMⅠ-Ⅱ期、中高分化、无微血管侵犯的患者;与miR-551b高表达的胆管癌患者比较,miR-551b低表达的胆管癌患者的总生存期明显缩短;miR-551b靶向cyclinD1基因mRNA 3’UTR的第1456-1462碱基、1479-1486碱基,胆管癌组织中cyclinD1的表达水平明显高于正常胆管组织且与miR-551b的表达具有负相关关系;术前CA19-9、TNM分期、微血管侵犯、miR-551b及cyclinD1表达是胆管癌患者总生存期的影响因素。结论胆管癌中miR-551表达减少与病理特征恶化、总生存期缩短相关,靶向cyclinD1是miR-551参与胆管癌发生发展的可能机制。

Objective To study the clinical significance of miR-551 b expressions in cholangiocarcinoma and analyze the target gene of mir-551 b by bioinformatics.Methods Seventy-eight patients with cholangiocarcinoma who underwent radical resection in our hospital between October 2014 and October 2018 were selected as the cholangiocarcinoma group while another 40 patients who underwent Roux-en-Y cholangiojejunostomy due to bile duct stones were selected as the control group.The expressions of miR-551 and cyclin D1 in cholangiocarcinoma and normal bile duct tissues were calculated and the overall survival(OS)of patients with cholangiocarcinoma was followed up.Results The expression of miR-551 b in cholangiocarcinoma tissues was lower than that in normal bile duct tissues.The expression of miR-551 b in cholangiocarcinoma tissues of patients with increased preoperative serum CA19-9 and CEA,in TNM stageⅢ,or with low-undifferentiated and microvascular invasion were significantly lower than that of patients with normal preoperative serum CA19-9 and CEA,in TNM stageⅠ-Ⅱ,or with medium-high differentiation and non-microvascular invasion.Compared with cholangiocarcinoma patients with high miR-551 b expressions,the overall survival of patients with low expressions of miR-551 b was significantly shortened.miR-551 b targeted 1456-1462 and 1479-1486 bases of mRNA 3′UTR of CyclinD1 gene,and the expression level of CyclinD1 in cholangiocarcinoma was significantly higher than that in the normal bile duct and negatively correlated with the expression of miR-551 b.Preoperative CA19-9,TNM stage,microvascular invasion,and expressions of miR-551 b and cyclinD1 were factors that influenced the overall survival of patients with cholangiocarcinoma.Conclusions The decrease of miR-551 expression in cholangiocarcinoma is related to the deterioration of pathological features and the shortening of total survival time.Targeting CyclinD1 is a possible mechanism by which miR-551 is involved in the occurrence and development of cholangiocarcinoma.