Huang Yongbiao, Chen Sheng, Qin Wan, Wang Yali, Li Long, Li Qianxia, Yuan Xianglin
Department of Oncology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, China.
Front Oncol. 2020 Oct 28;10:580513. doi: 10.3389/fonc.2020.580513. eCollection 2020.
Hepatocellular carcinoma (HCC) is a highly malignant and aggressive cancer with high recurrence rates and mortality. Some studies have illustrated that RNA binding proteins (RBPs) were involved in the carcinogenesis and development of multiple cancers, but the roles in HCC were still unclear. We downloaded the RNA-seq and corresponding clinical information of HCC from The Cancer Genome Atlas (TCGA) database, and 330 differentially expressed RBPs were identified between normal and HCC tissues. Through series of the univariate, the least absolute shrinkage selection operator (LASSO), and the stepwise multivariate Cox regression analyses, six prognosis-related key RBPs (CNOT6, UPF3B, MRPL54, ZC3H13, IFIT5, and PPARGC1A) were screened out from DE RBPs, and a six-RBP gene risk score signature was constructed in training set. Survival analysis indicated that HCC patients with high-risk scores had significantly worse overall survival than low-risk patients, and furthermore, the signature can be used as an independent prognostic indicator. The good accuracy of this prognostic signature was confirmed by the ROC curve analysis and was further validated in the International Cancer Genome Consortium (ICGC) HCC cohort. Besides, a nomogram based on six RBP genes was established and internally validated in the TCGA cohort. Gene set enrichment analysis demonstrated some cancer-related phenotypes were significantly gathered in the high-risk group. Overall, our study first identified an RBP-related six-gene prognostic signature, which could serve as a promising prognostic biomarker and provide some potential therapeutic targets for HCC.
肝细胞癌(HCC)是一种高度恶性且侵袭性强的癌症,复发率和死亡率都很高。一些研究表明,RNA结合蛋白(RBPs)参与了多种癌症的发生和发展,但在HCC中的作用仍不清楚。我们从癌症基因组图谱(TCGA)数据库下载了HCC的RNA测序数据及相应的临床信息,在正常组织和HCC组织之间鉴定出330个差异表达的RBPs。通过一系列单变量、最小绝对收缩选择算子(LASSO)和逐步多变量Cox回归分析,从差异表达的RBPs中筛选出六个与预后相关的关键RBPs(CNOT6、UPF3B、MRPL54、ZC3H13、IFIT5和PPARGC1A),并在训练集中构建了一个六RBPs基因风险评分特征。生存分析表明,高风险评分的HCC患者总生存期明显低于低风险患者,此外,该特征可作为独立的预后指标。ROC曲线分析证实了该预后特征具有良好的准确性,并在国际癌症基因组联盟(ICGC)的HCC队列中进一步验证。此外,基于六个RBP基因建立了列线图,并在TCGA队列中进行了内部验证。基因集富集分析表明,一些癌症相关表型在高风险组中显著聚集。总体而言,我们的研究首次鉴定出一种与RBP相关的六基因预后特征,它可作为一种有前景的预后生物标志物,并为HCC提供一些潜在的治疗靶点。