胆管细胞癌患者中miR-320a和GP73表达及预后研究

肝癌电子杂志 ›› 2020, Vol. 7 ›› Issue (2): 16-20.

胆管细胞癌患者中miR-320a和GP73表达及预后研究

张雷^1,*, 孙景武², 张佳兴³

1 河北中石油中心医院普通外科,河北廊坊 065000;
2 河北中石油中心医院肝胆外科,河北廊坊065000;
3 廊坊市妇幼保健中心,河北廊坊065099

收稿日期:2020-05-12 出版日期:2020-06-30 发布日期:2020-07-23
通讯作者: ^* 张雷 E-mail: zhle0402@sina.com
作者简介:张雷,主治医师,河北中石油中心医院普通外科。
基金资助:
河北省廊坊市科技支撑计划第三批指令项目（2015013009c）

Study on the expression and prognosis of miR-320a and GP73 in patients with cholangiocarcinoma

Zhang Lei^1,*, Sun Jingwu², Zhang Jiaxing³

1 Department of General Surgery, Hebei Petro China Center Hospital , Langfang 065000, Hebei, China;
2 Department of Hepatobiliary Surgery, Hebei Petro China Center Hospital, Langfang 065000, Hebei, China;
3 Langfang Maternal and Child Health Center, Langfang 065099, Hebei, China

Received:2020-05-12 Online:2020-06-30 Published:2020-07-23

摘要/Abstract

摘要： 目的: 观察胆管细胞癌患者中微小RNA-320a（miR-320a）、高尔基体膜蛋白73（GP73）协同作用及预后研究。方法: 选取2014年6月至2018年12月本院收治的胆管细胞癌患者142例为胆管细胞癌组,并选取同时间段内本院健康体检者146例为健康组。以实时荧光定量法（qRT-PCR）检测两组血清miR-320a表达水平;以酶联免疫吸附法测定(enzyme-linked immunosorbent assay,ELISA）两组GP73表达水平;分析胆管细胞癌组患者血清中miR-320a、GP73表达水平与胆管细胞癌临床特征及miR-320a表达水平与GP73关系;分析胆管细胞癌预后的影响因素;分析血清miR-320a、GP73表达水平对胆管细胞癌的诊断价值。结果: 胆管细胞癌组患者血清miR-320a表达水平明显低于健康组（P<0.05）,GP73水平明显高于健康组（P<0.05）;胆管细胞癌组患者血清miR-320a、GP73表达水平均与血管浸润、TNM分期、肝硬化有关（均P<0.05）;胆管细胞癌患者血清中miR-320a表达水平与GP73呈负相关（P<0.05）;血管浸润、TNM分期、肝硬化、GP73为胆管细胞癌预后的危险因素（P<0.05),miR-320a为胆管细胞癌预后的保护因素（P<0.05);血清miR-320a、GP73表达水平诊断胆管细胞癌的曲线下面积（area under curve,AUC）分别为0.875、0.878,对应灵敏度分别为84.5%、85.4%,特异度分别为79.5%、79.5%;血清miR-320a、GP73联合诊断胆管细胞癌的AUC为0.956,其灵敏度、特异度分别为90.8%、91.8%。结论: 胆管细胞癌患者血清中miR-320a低表达,GP73高表达,miR-320a与GP73具有一定负相关性,两者可能通过相互作用,进而共同影响胆管细胞癌发生发展。

关键词: 微小RNA-320a, 高尔基体膜蛋白73, 胆管细胞癌, 表达关系, 预后

Abstract: Objective: To observe the synergistic effect and prognosis of microRNA-320a (miR-320a) and Golgi protein 73 (GP73) in patients with cholangiocarcinoma.Methods: 142 patients with cholangiocarcinoma admitted to our hospital from June 2014 to December 2018 were selected as cholangiocarcinoma group, and 146 cases of physical examination were selected as healthy group during the same period. The expression level of serum miR-320a in the two groups was detected real-time fluorescence quantitative assay (qRT-PCR); the expression level of GP73 in the two groups was determined by enzyme-linked immunosorbent assay (ELISA); the relationships between the expression levels of serum miR-320a, GP73 with clinical characteristics of cholangiocarcinoma and the relationship between expression levels of miR-320a and GP73 were analyzed; the prognostic factors of cholangiocarcinoma were analyzed; and the diagnostic values of levels of serum miR-320a and GP73 in cholangiocarcinoma were analyzed.Results: The expression level of serum miR-320a in cholangiocarcinoma group was significantly lower than that in healthy group (P < 0.05), and the level of GP73 was significantly higher than that in healthy group (P < 0.05); the expression levels of serum miR-320a and GP73 in cholangiocarcinoma group were correlated with vascular invasion, TNM stage and cirrhosis (all P< 0.05); the expression level of miR-320a was negatively correlated with GP73 in patients with cholangiocarcinoma (P< 0.05); vascular invasion, TNM stage, cirrhosis and GP73 were risk factors for the prognosis of cholangiocarcinoma (P< 0.05), and miR-320a was protective factor for the prognosis of cholangiocarcinoma (P< 0.05); the areas under curve (AUC) of the expression levels of serum miR-320a and GP73 in diagnosis of cholangiocarcinoma were 0.875 and 0.878, respectively, the corresponding sensitivities were 84.5% and 85.4% respectively, and the specificities were 79.5% and 79.5% respectively; the AUC of combined diagnosis of serum miR-320a and GP73 for cholangiocarcinoma was 0.956, and the sensitivity and specificity were 90.8% and 91.8% respectively.Conclusions: The expression of serum miR-320a in patients with cholangiocarcinoma is low, and GP73 is high, there is a negative correlation between miR-320a and GP73, and the interaction between them may affect the occurrence and development of cholangiocarcinoma.

Key words: MicroRNA-320a, Golgi protein 73, Cholangiocarcinoma, Expression relationship, Prognosis

张雷, 孙景武, 张佳兴. 胆管细胞癌患者中miR-320a和GP73表达及预后研究[J]. 肝癌电子杂志, 2020, 7(2): 16-20.

Zhang Lei, Sun Jingwu, Zhang Jiaxing. Study on the expression and prognosis of miR-320a and GP73 in patients with cholangiocarcinoma[J]. Electronic Journal of Liver Tumor, 2020, 7(2): 16-20.

参考文献

[1] ZHANG C, GE CL.A Simple Competing Endogenous RNA Network Identifies Novel mRNA, miRNA, and lncRNA Markers in Human Cholangiocarcinoma[J]. Biomed Res Int, 2019, 2019:3526407.
[2] LIU HB, MA LJ, WANG J.Overexpression of miR-25 is associated with progression and poor prognosis of cholangiocarcinoma[J]. Exp Ther Med, 2019, 18(4):2687-2694.
[3] 吕晓婷, 熊伟, 宋丹, 等. MiR-320a在肝癌中的表达及对SMMC-7721肝癌细胞凋亡和迁移的影响[J]. 基因组学与应用生物学, 2018, 37(5):2305-2311.
[4] KE MY, WU XN, ZHANG Y, et al.Serum GP73 predicts posthepatectomy outcomes in patients with hepatocellular carcinoma[J]. J Transl Med, 2019, 17(1):140-149.
[5] 陈亚进, 商昌珍. 肝内胆管细胞癌诊治策略[J]. 中国实用外科杂志, 2015, 35(1):43-45.
[6] LABIB PL, GOODCHILD G, PEREIRA SP.Molecular Pathogenesis of Cholangiocarcinoma[J]. BMC Cancer, 2019, 19(1):185-200.
[7] BLECHACZ B.Cholangiocarcinoma: Current Knowledge and New Developments[J]. Gut Liver, 2017, 11(1):13-26.
[8] MOTTI ML, D ANGELO S, MECCARIELLO R. MicroRNAs, Cancer and Diet: Facts and New Exciting Perspectives[J]. Curr Mol Pharmacol, 2018, 11(2):90-96.
[9] LV YX, DUANMU JZ, FU XR, et al.Identifying a new microRNA signature as a prognostic biomarker in colon cancer[J]. PLoS One, 2020, 15(2):e0228575
[10] WU JB, YANG B, ZHANG YP, et al.miR-424-5p represses the metastasis and invasion of intrahepatic cholangiocarcinoma by targeting ARK5[J]. Int J Biol Sci, 2019, 15(8):1591-1599.
[11] CHANG WP, WANG Y, LI WZ, et al.MicroRNA-551b-3p inhibits tumour growth of human cholangiocarcinoma by targeting Cyclin D1[J]. J Cell Mol Med, 2019, 23(8):4945-4954.
[12] LI YY, LIU HJ, SHAO JP, et al.miR-320a serves as a negative regulator in the progression of gastric cancer by targeting RAB14[J]. Mol Med Rep, 2017, 16(3):2652-2658.
[13] LU CC, LIAO ZW, CAI MX, et al.MicroRNA-320a downregulation mediates human liver cancer cell proliferation through the Wnt/β-catenin signaling pathway[J]. Oncol Lett, 2017, 13(2):573-578.
[14] 刘丽萍, 陈健康, 刘元明, 等. 高尔基体蛋白73在肝细胞癌转移及侵袭中的作用[J]. 中华肿瘤杂志, 2017, 39(7):497-501.
[15] ZHANG ZG, ZHANG YY, WANG YY, et al.Alpha-fetoprotein-L3 and Golgi protein 73 may serve as candidate biomarkers for diagnosing alpha-fetoprotein-negative hepatocellular carcinoma[J]. Onco Targets Ther, 2015, 9(12):123-129.
[16] 郑绪斌, 李永慧, 陈志桥. GP73在肝癌中的诊断价值[J]. 热带医学杂志, 2017, 17(2):68-70.
[17] 黄健, 蒋贝格, 杨远, 等. 根治性手术切除治疗早期胆管细胞癌的预后影响因素分析[J]. 临床肝胆病杂志, 2018, 34(10):125-131.