MEP1A Contributes to Tumor Progression and Predicts Poor Clinical Outcome in Human Hepatocellular Carcinoma
MEP1A Contributes to Tumor Progression and Predicts Poor Clinical Outcome in Human Hepatocellular Carcinoma
复制标题
MEP1A 促进肿瘤进展并预测人类肝细胞癌的不良临床结果
DOI：
10.1002/hep.28397
复制
发表时间：
2016-04-01
期刊：
影响因子：
13.5
通讯作者：
Shi, Ming
中科院分区：
文献类型：
--
作者：
OuYang, Han-Yue;Xu, Jing;Shi, Ming
尽管已针对肝细胞癌（HCC）提出了许多分期分类，但由于HCC的分子多样性，在临床实践中确定患者的预后是一项挑战。我们研究了MEP 1A（一种候选癌基因）与HCC患者临床结局之间的关系;此外，我们还探讨了MEP 1A在HCC中的作用。在这份报告中，它是通过定量实时聚合酶链反应表明，MEP 1A信使RNA水平显着升高，在肝癌肿瘤组织与匹配的相邻非肿瘤组织和非恶性肝病组织相比。对来自两个独立组的394名HCC患者的组织样本的免疫组织化学分析显示，在两个队列1中，肿瘤细胞中MEP 1A的阳性表达是影响根治性切除术后生存率的独立且重要的危险因素（风险比= 2.05，95%置信区间1.427-2.946; P < 0.001）和队列2（风险比= 1.89，95%置信区间1.260-2.833; P = 0.002）。巴塞罗那临床肝癌0-A期亚组的分析进一步显示，肿瘤细胞中MEP 1A表达阳性的患者比肿瘤细胞中MEP 1A表达阴性的患者具有较差的手术预后（队列1 P = 0.001，队列2 P < 0.001）。体外和体内实验均表明，MEP 1A促进HCC细胞增殖、迁移和侵袭。进一步分析发现，MEP 1A在调节细胞骨架事件和诱导HCC细胞的上皮-间质转化中起重要作用。结论：MEP 1A是一种新的肝癌预后预测因子，在肝癌的发生、发展中起重要作用。
Although many staging classifications have been proposed for hepatocellular carcinoma (HCC), determining a patient's prognosis in clinical practice is a challenge due to the molecular diversity of HCC. We investigated the relationship between MEP1A, a candidate oncogene, and clinical outcomes of HCC patients; furthermore, we explored the role of MEP1A in HCC. In this report, it was demonstrated by quantitative real-time polymerase chain reaction that MEP1A messenger RNA levels were significantly elevated in HCC tumor tissues compared with matched adjacent nonneoplastic tissues and nonmalignant liver disease tissues. Immunohistochemical analyses of tissue samples from two independent groups of 394 HCC patients showed that positive expression of MEP1A in tumor cells was an independent and significant risk factor affecting survival after curative resection in both cohort 1 (hazard ratio = 2.05, 95% confidence interval 1.427-2.946; P < 0.001) and cohort 2 (hazard ratio = 1.89, 95% confidence interval 1.260-2.833; P = 0.002). Analysis of Barcelona Clinic Liver Cancer stage 0-A subgroup further showed that patients with positive MEP1A expression in tumor cells had poorer surgical prognoses than those with negative MEP1A expression in tumor cells (cohort 1 P = 0.001, cohort 2 P < 0.001). Both in vitro and in vivo assays showed that MEP1A promoted HCC cell proliferation, migration, and invasion. Further analyses found that MEP1A played an important role in regulating cytoskeletal events and induced epithelial-mesenchymal transition in HCC cells. Conclusion: MEP1A is a novel prognostic predictor in HCC and plays an important role in the development and progression of HCC.