Patients with renal cell carcinoma (RCC) usually develop drug resistance and have poor prognosis owing to its insensitive property. However, the underlying mechanisms of RCC are still unclear. We implemented an integrative analysis of The Cancer Genome Atlas and Gene Expression Omnibus datasets. Three genes (CRHBP, RAB25 and PSAT1) were found to be potential biomarkers in ccRCC and validated by four independent cohorts. Then, ccRCC patients with a decreased expression of CRHBP in tumor tissues had significantly poor survival by TCGA ccRCC datasets and verified by clinical samples as well as RCC cell lines. Overexpression of CRHBP suppressed cell proliferation, migration, invasion as well as apoptosis in vitro and in vivo. Moreover, the results of western blot analysis showed the effects of CRHBP via upregulating NF-κB and p53-mediated mitochondria apoptotic pathway. Our results suggested that CRHBP may be an effective target to treat ccRCC patients.

肾细胞癌（RCC）患者由于其不敏感的特性，通常会产生耐药性并且预后不良。然而，RCC的潜在机制仍不清楚。我们对癌症基因组图谱和基因表达综合数据集进行了综合分析。发现三个基因（CRHBP、RAB2​​5 和 PSAT1）是 ccRCC 中的潜在生物标志物，并由四个独立队列验证。然后，通过 TCGA ccRCC 数据集并通过临床样本和 RCC 细胞系验证，肿瘤组织中 CRHBP 表达降低的 ccRCC 患者的存活率显着降低。CRHBP 的过表达在体外和体内抑制细胞增殖、迁移、侵袭以及细胞凋亡。而且，Western印迹分析结果显示CRHBP通过上调NF-κB和p53介导的线粒体凋亡途径发挥作用。我们的研究结果表明，CRHBP 可能是治疗 ccRCC 患者的有效靶点。