MDM4表达在肾细胞癌中的临床相关性与作用研究

Expression of MDM4 and its clinical significance and role in renal cell carcinoma

目的:通过研究肾细胞癌(RCC)组织MDM4的mRNA和蛋白表达水平,分析其与RCC临床病理特征的相关性,并利用细胞系研究MDM4对RCC细胞迁移和侵袭能力的作用,探讨其潜在的作用。方法:选取2014年1月~2017年2月在我院行手术切除治疗的RCC组织标本82例和癌旁组织标本20例为研究对象,应用实时荧光定量PCR和Western blot分别检测MDM4的表达水平。收集患者性别、年龄、病理分级等临床病理资料,并分析其与MDM4mRNA表达的相关性。体外应用RCC细胞系研究MDM4对RCC细胞迁移和侵袭能力的影响。结果:与癌旁组织相比,MDM4 mRNA和蛋白在RCC组织中表达显著上调。统计学分析发现,MDM4mRNA的表达与RCC病理TNM分期和远隔转移呈正相关(P<0.01)。肿瘤细胞系ACHN细胞中MDM4表达显著高于其他肿瘤细胞系及人正常肾小管上皮细胞HK-2(P<0.01)。体外沉默MDM4显著抑制ACHN的细胞增殖、迁移和侵袭。结论:MDM4表达与RCC的恶性特征及癌细胞增殖、迁移和侵袭能力密切相关,有望成为RCC的潜在治疗靶点。

Objective:By studying the mRNA and protein expression levels of MDM4 in renal cell carcinoma,the correlation between the expression of MDM4 and the clinicopathological features of renal cell carcinoma was analyzed.The effect of MDM4 on the migration and invasion of renal cell carcinoma cells was also studied using cell lines to explore its potential role.Method:From January 2014 to February 2017,tumor samples from 82 patients with renal cell carcinoma who were treated with surgical resection and 20 adjacent samples at the first Affiliated Hospital of Henan University of Science and Technology were collected.The real-time fluorescence quantitative PCR and Western blot were utilized to detect the expression of MDM4.The clinicopathologic data including sex,age and pathological grade were collected and analyzed for their associations with MDM4 mRNA expression.Effects of MDM4 on migration and invasion of renal cell carcinoma cells in vitro were studied using renal cell carcinoma cell lines.Result:Compared with adjacent tissues,the expression of MDM4 mRNA and protein significantly up-regulated in renal cell carcinoma samples.Statistical analysis showed that the expression of MDM4 mRNA was positively correlated with TNM staging and metastasis of renal cell carcinoma(P <0.01).The expression of MDM4 in tumor cell line ACHN was significantly higher than that in other tumor cell lines and normal renal tubular epithelial cells HK-2(P<0.01).In vitro silencing of MDM4 significantly inhibited ACHN cell proliferation,migration and invasion.Conclusion:MDM4 expression is closely related to the malignant features of renal cell carcinoma and the proliferation,migration and invasion of cancer cells,which is expected to be a potential therapeutic target for renal cell carcinoma.