Zhu Zhenpeng, He Anbang, Lin Lanruo, Xu Chunru, Cai Tianyu, Lin Jian
Department of Urology, Peking University First Hospital, Beijing 100034, China.
Institute of Urology, Peking University, Beijing 100034, China.
J Cancer. 2020 Sep 23;11(22):6591-6600. doi: 10.7150/jca.49175. eCollection 2020.
Early detection and accurate evaluation were both critical to improving the prognosis of clear cell Renal Cell Carcinoma (ccRCC) patients. More importantly, RNA Binding Proteins (RBPs) play a vital role in the tumorigenesis and progression of numerous cancers. However, the relationship between RBPs and ccRCC is still unclear. Exploring the potential biological functions of RBPs in ccRCC and establishing a prognostic signature to predict the survival probability remains meaningful. In this study, transcriptome profiling and the corresponding clinical information were obtained from the TCGA database, GEO database, and ICGC database. By using the "edgeR" R package, 200 DERBPs were found, including 128 up-regulated and 72 down-regulated RBPs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DERBPs were mainly involved in regulating transcriptional processes and metabolism. Furthermore, there were 4 hub genes (RPS2, RPS14, RPS20, and RPLP0) were found in the PPI network, which may play vital biological roles among those DERBPs. Then we used LASSO regression to construct a prognostic signature and validated the signature in the GEO and ICGC cohort. The time-dependent receiver operating characteristic (ROC) curve showed that the signature could accurately predict the prognosis of ccRCC patients. Then we established a nomogram, and the calibration curve and ROC curve showed that the nomogram could accurately predict 1-year, 3-year, and 5-year overall survival (OS) of ccRCC patients (The AUC value: 0.871, 0.829, and 0.816). In conclusion, we constructed a 10-RBPs-based prognostic signature integrating clinical parameters to predict the prognosis of ccRCC patients. The prognostic signature based on the differentially expressed RBPs (DERBPs) might serve as promising diagnostic and prognostic biomarkers in ccRCC.
早期检测和准确评估对于改善透明细胞肾细胞癌（ccRCC）患者的预后都至关重要。更重要的是，RNA结合蛋白（RBPs）在众多癌症的发生和发展中起着至关重要的作用。然而，RBPs与ccRCC之间的关系仍不清楚。探索RBPs在ccRCC中的潜在生物学功能并建立预测生存概率的预后特征仍然具有重要意义。在本研究中，从TCGA数据库、GEO数据库和ICGC数据库中获取了转录组谱和相应的临床信息。通过使用“edgeR”R包，发现了200个差异表达的RBPs（DERBPs），包括128个上调的和72个下调的RBPs。基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析表明，DERBPs主要参与调节转录过程和代谢。此外，在蛋白质-蛋白质相互作用（PPI）网络中发现了4个核心基因（RPS2、RPS14、RPS20和RPLP0），它们可能在这些DERBPs中发挥重要的生物学作用。然后我们使用LASSO回归构建了一个预后特征，并在GEO和ICGC队列中对该特征进行了验证。时间依赖性受试者工作特征（ROC）曲线表明，该特征可以准确预测ccRCC患者的预后。然后我们建立了一个列线图，校准曲线和ROC曲线表明，该列线图可以准确预测ccRCC患者1年、3年和5年的总生存期（OS）（AUC值分别为0.871、0.829和0.816）。总之，我们构建了一个基于10个RBPs的预后特征，并整合了临床参数来预测ccRCC患者的预后。基于差异表达RBPs（DERBPs）的预后特征可能作为ccRCC中有前景的诊断和预后生物标志物。
