Shen Tao, Wang Meiting, Wang Xiangting
Department of Geriatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, 230026, China.
College of Liren, Yanshan University, Qinhuangdao, 066004, China.
J Cancer. 2021 Feb 22;12(8):2230-2242. doi: 10.7150/jca.52156. eCollection 2021.
RNA binding proteins (RBPs) are dysregulated and associated with the occurrence and development in various malignant tumors. However, the role of RBPs in tongue cancer are largely unclear. Here, by integrating the differential gene expression analysis and the Weighted Gene Co-expression Network Analysis (WGCNA) of TCGA-retrieved RNA-seq data, we identified a total of 171 differential co-expression RBPs. Then, in a protein-protein interaction (PPI) network containing 134 nodes (RBPs) and 315 network edges (RBP-RBP interacting networks), the top 30 hub RBPs were identified using the CytoHubba plugin of Cytoscape. Furthermore, we investigated the expression and prognostic value of these RBPs and their highly correlated networks. Among them, six RBPs (PGK1, SLC20A1, LEPR, CYP19A1, ZC3H12D, and PFKM) were shown to be the prognosis-related hub RBPs (prhRBPs). Based on these hub RBPs, we constructed a prognostic model and found that the patients in the high-risk group had dramatically poor overall survival compared to those in low-risk group. In addition, we validated the prognostic model in GSE41613, another tongue cancer patient cohort from GEO datasets. The time-dependent receiver operating characteristic (ROC) analysis of the prognostic model further confirmed the predictive capability of the risk model for tongue cancer. As suggested in functional annotation analysis, we found an intensive enrichment of these prhRBPs in metabolic pathways, including AMPK, HIF-1 signaling pathway, Glycolysis, and steroid hormone biosynthesis. Together, our study revealed the underlying role of RBP in tongue cancer biology and potentially unveiled novel targets for cancer therapy.
RNA结合蛋白（RBPs）失调并与各种恶性肿瘤的发生和发展相关。然而，RBPs在舌癌中的作用在很大程度上尚不清楚。在这里，通过整合从TCGA获取的RNA测序数据的差异基因表达分析和加权基因共表达网络分析（WGCNA），我们总共鉴定出171个差异共表达的RBPs。然后，在一个包含134个节点（RBPs）和315条网络边（RBP-RBP相互作用网络）的蛋白质-蛋白质相互作用（PPI）网络中，使用Cytoscape的CytoHubba插件鉴定出前30个核心RBPs。此外，我们研究了这些RBPs及其高度相关网络的表达和预后价值。其中，六个RBPs（PGK1、SLC20A1、LEPR、CYP19A1、ZC3H12D和PFKM）被证明是与预后相关的核心RBPs（prhRBPs）。基于这些核心RBPs，我们构建了一个预后模型，发现高危组患者的总生存期明显低于低危组患者。此外，我们在来自GEO数据集的另一个舌癌患者队列GSE41613中验证了该预后模型。预后模型的时间依赖性受试者工作特征（ROC）分析进一步证实了风险模型对舌癌的预测能力。正如功能注释分析所表明的，我们发现这些prhRBPs在代谢途径中高度富集，包括AMPK、HIF-1信号通路、糖酵解和类固醇激素生物合成。总之，我们的研究揭示了RBP在舌癌生物学中的潜在作用，并可能揭示癌症治疗的新靶点。
