Zhu Rui, Li Xiezhao, Cai Zhiduan, Liang Siyang, Yuan Yaoji, Xu Yuyu, Lai Dehui, Zhao Haibo, Yang Weiqing, Bian Jun, Liu Leyuan, Xu Guibin
Department of Urology, The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Oncol. 2021 Oct 25;11:726671. doi: 10.3389/fonc.2021.726671. eCollection 2021.
Clear cell renal cell carcinoma (ccRCC) carrying wild-type Von Hippel-Lindau (VHL) tumor suppressor are more invasive and of high morbidity. Concurrently, competing endogenous RNA (ceRNA) network has been suggested to play an important role in ccRCC malignancy. In order to understand why the patients carrying wild-type VHL gene have high degrees of invasion and morbidity, we applied bioinformatics approaches to identify 861 differentially expressed RNAs (DE-RNAs) between patients carrying wild-type and patients carrying mutant VHL from The Cancer Genome Atlas (TCGA) database, established a ceRNA network including 122 RNAs, and elected six survival-related DE-RNAs including Linc00942, Linc00858, RP13_392I16.1, hsa-miR-182-5p, hsa-miR-183-5p, and PAX3. Examining clinical samples from our hospital revealed that patients carrying wild-type VHL had significantly higher levels of all six RNAs than those carrying mutant VHL. Patients carrying wild-type VHL had significantly higher risk scores, which were calculated based on expression levels of all six RNAs, than those carrying mutant VHL. Patients with higher risk scores had significantly shorter survival times than those with lower risk scores. Therefore, the risk scores serve well to predict malignancy and prognosis.
携带野生型冯·希佩尔-林道(VHL)肿瘤抑制基因的透明细胞肾细胞癌(ccRCC)侵袭性更强且发病率更高。同时,有研究表明竞争性内源RNA(ceRNA)网络在ccRCC的恶性进展中起重要作用。为了弄清楚携带野生型VHL基因的患者为何具有高度侵袭性和高发病率,我们运用生物信息学方法从癌症基因组图谱(TCGA)数据库中鉴定出861个在携带野生型VHL基因的患者和携带突变型VHL基因的患者之间差异表达的RNA(DE-RNA),建立了一个包含122个RNA的ceRNA网络,并选出6个与生存相关的DE-RNA,包括Linc00942、Linc00858、RP13_392I16.1、hsa-miR-182-5p、hsa-miR-183-5p和PAX3。对我院临床样本的检测显示,携带野生型VHL基因的患者这6种RNA的水平均显著高于携带突变型VHL基因的患者。基于这6种RNA的表达水平计算得出,携带野生型VHL基因的患者风险评分显著高于携带突变型VHL基因的患者。风险评分较高的患者生存时间显著短于风险评分较低的患者。因此,风险评分能很好地预测恶性程度和预后。