Xiao Wen, Wang Xuegang, Wang Tao, Xing Jinchun
Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China,
Cancer Manag Res. 2018 Nov 20;10:5951-5964. doi: 10.2147/CMAR.S185270. eCollection 2018.
Tripartite motif containing (TRIM) family protein has been involved in multiple pathogenesis of cancers. TRIM2 is a member of the family, and its role in clear cell renal cell carcinoma (ccRCC) remains to be unclarifid. Here, we showed the clinical value and biological role of TRIM2 in ccRCC.
ROC curves analyzed the clinicopathological parameters, Kaplan-Meier survival analysis determined the correlation of OS and DFS time, multivariate analysis demonstrated the prognostic indicator in overall survival and disease-free survival of ccRCC with TRIM2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database. Western blotting and immunohistochemistry were used to check the level of TRIM2 expression. Gain-of-function assay by exogenous overexpression of TRIM2 studied the biological role of TRIM2 in renal cell carcinoma cells.
TRIM2 expression was associated with various clinicopathologicalfactors and lower TRIM2 expression was interrelated to a poor prognosis. The levels of TRIM2 expression were also scanty in ccRCC tissues and renal cancer cell lines than in normal control. The biological role of TRIM2 in ccRCC was identifid by bioinformatics analysis and functional analysis. Exogenous overexpression of TRIM2 with the gain-of-function assay in renal cell carcinoma cells showed that the cell proliferation, migration, and invasion were signifiantly suppressed.
These results showed that TRIM2 acted as an antitumor gene and a specifi prognostic indicator for patients with ccRCC, which indicated that positive modulation of TRIM2 might be a novel treatment strategy for ccRCC.
含三联基序（TRIM）家族蛋白参与了癌症的多种发病机制。TRIM2是该家族的成员之一，其在肾透明细胞癌（ccRCC）中的作用尚待阐明。在此，我们展示了TRIM2在ccRCC中的临床价值和生物学作用。
ROC曲线分析临床病理参数，Kaplan-Meier生存分析确定总生存期（OS）和无病生存期（DFS）时间的相关性，多变量分析在癌症基因组图谱肾透明细胞癌（TCGA-KIRC）数据库中证实TRIM2表达是ccRCC总生存期和无病生存期的预后指标。采用蛋白质免疫印迹法和免疫组织化学法检测TRIM2的表达水平。通过外源性过表达TRIM2进行功能获得实验，研究TRIM2在肾癌细胞中的生物学作用。
TRIM2表达与多种临床病理因素相关，TRIM2低表达与预后不良相关。与正常对照相比，ccRCC组织和肾癌细胞系中TRIM2的表达水平也较低。通过生物信息学分析和功能分析确定了TRIM2在ccRCC中的生物学作用。在肾癌细胞中通过功能获得实验外源性过表达TRIM2，结果显示细胞增殖、迁移和侵袭均受到显著抑制。
这些结果表明，TRIM2作为一种抗肿瘤基因，是ccRCC患者的特异性预后指标，这表明对TRIM2进行正向调控可能是ccRCC的一种新的治疗策略。
