miRNA-149表达变化对肝细胞癌患者预后的影响及潜在机制探索

摘要/Abstract

摘要： 目的探讨miRNA-149表达水平变化对肝细胞癌患者预后的影响及潜在机制。方法从TCGA数据库选取344例肝细胞癌患者临床及基因组数据,按照miRNA-149表达水平的高低分为高表达组（n = 172）和低表达组（n = 172）。绘制两组患者生存曲线,并分别比较肿瘤分期不同的患者体内miRNA-149的相对表达水平差异。各选取与miRNA-149正、负相关系数最高的前50个基因进行生物学注释、分类和编码蛋白之间的相互作用分析。另取32例肝细胞癌患者肿瘤样本,RT-PCR法检测miRNA-149、谷氨酸脱氢酶1（GLUD1）和羟基类固醇17-β脱氢酶4（HSD17B4）的表达水平,比较不同分期患者miRNA-149表达差异。将32例患者分为miRNA-149高表达组（H组）和低表达组（L组）,比较两组患者临床数据差异。结果 miRNA-149低表达组患者的中位生存时间长于miRNA-149高表达组,差异有统计学意义（2532d比1271d,P<0.001）。根据病理分期进行分组,I期患者miRNA-149表达水平显著低于Ⅱ、Ⅲ期的患者（P<0.05）。根据T分期进行分组,其中T1期患者miRNA-149表达水平显著低于T2、T3期患者（P<0.05）。miRNA-149相关基因主要涉及的生物学过程为生物调节;主要涉及的分子功能为蛋白质结合;主要涉及的细胞组分为细胞膜,主要涉及的信号通路为细胞外基质代谢通路。GLUD1和HSD17B4是处于相关基因编码蛋白之间的相互作用网络核心的蛋白。与H组比较,L 组GLUD1和HSD17B4基因表达均较高（P<0.05）。临床样本中不同分期患者miRNA-149表达水平差异有统计学意义（P = 0.019）,其中Ⅲ 期患者miRNA-149表达水平显著高于I期或Ⅱ期患者（P<0.05）。结论 miRNA-149高表达与肝细胞癌患者远期预后不良有关,这可能与其靶向调控谷氨酸及雌二醇代谢通路有关。

关键词: 肝细胞癌, 微小RNA149, 预后

Abstract: Objective: To explore the effect of miRNA-149 expression on the prognosis of patients with hepatocellular carcinoma (HCC) and its potential mechanism. Methods: Clinical and genomic data of 344 patients with hepatocellular carcinoma was selected from TCGA database. According to the level of miRNA-149 expression, the patients were divided into two groups: high expression group (n = 172) and low expression group (n = 172). The survival curves of the two groups were drawn, and the relative expression levels of miRNA-149 in patients with different tumor stages were compared. The top 50 genes with the highest positive and negative correlation coefficients with miRNA-149 were selected for biological annotation, classification and interaction analysis of encoded proteins. The expression levels of miRNA-149, glutamate dehydrogenase 1 (GLUD1) and hydroxysteroid 17-β dehydrogenase 4 (HSD17B4) were detected by RT-PCR in 32 patients with hepatocellular carcinoma. The differences of miRNA-149 expression in patients with different stages were compared. 32 patients were divided into high miRNA-149 expression group (group H) and low expression group (group L). The clinical data of the two groups were compared. Results: The median survival time of patients with low expression of miRNA-149 was longer than that of patients with high expression of miRNA-149, and the difference was statistically significant (2532 d vs.1271 d P<0.001). According to the pathological stage, the expression level of miRNA-149 in stage I was significantly lower than that in stageⅡ andⅢ (P<0. 05). According to T stage, the expression level of miRNA-149 in T1 stage was significantly lower than that in T2 and T3 stage (P<0. 05). The main biological processes involved in miRNA-149-related genes are biological regulation. The main molecular functions involved are protein binding. The main cell components involved are cell membrane. The main signal pathways involved are extracellular matrix metabolic pathway. GLUD1 and HSD17B4 are proteins at the core of the interaction network between related genes. Compared with group H, the expression of GLUD1 and HSD17B4 genes in group L was significantly higher than that in group H (P<0.05). There was significant difference in the expression level of miRNA-149 among different stages of clinical samples (P = 0.019). The expression level of miRNA-149 in patients with stage Ⅲ was significantly higher than that in patients with stage Ⅰ or Ⅱ (P<0.05). Conclusion: The high expression of miRNA-149 is related to the poor long-term prognosis of HCC, which may be related to its targeted regulation of glutamate and estradiol metabolic pathway.

Key words: Hepatocellular carcinoma, MiRNA-149, Prognosis

金晓新, 何世林, 高琰妍, 于晓双, 王振国, 侯世科. miRNA-149表达变化对肝细胞癌患者预后的影响及潜在机制探索[J]. 肝癌电子杂志, 2020, 7(3): 30-35.

Jin Xiaoxin, He Shilin, Gao Yanyan, Yu Xiaoshuang, Wang Zhenguo, Hou Shike. Effect of miRNA-149 expression on the prognosis of patients with hepatocellular carcinoma and its potential mechanism[J]. Electronic Journal of Liver Tumor, 2020, 7(3): 30-35.

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