Department of Plastic and Burn Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Technol Cancer Res Treat. 2021 Jan-Dec;20:15330338211004936. doi: 10.1177/15330338211004936.
Dysregulation of RNA binding proteins (RBPs) has been identified in multiple malignant tumors correlated with tumor progression and occurrence. However, the function of RBPs is not well understood in hepatocellular carcinoma (HCC).
The RNA sequence data of HCC was extracted out of the Cancer Genome Atlas (TCGA) database and different RBPs were calculated between regular and cancerous tissue. The study explored the expression and predictive value of the RBPs systemically with a series of bioinformatic analyzes.
A total of 330 RBPs, including 208 up-regulated and 122 down-regulated RBPs, were classified differently. Four RBPs (MRPL54, EZH2, PPARGC1A, EIF2AK4) were defined as the forecast related hub gene and used to construct a model for prediction. Further study showed that the high-risk subgroup is poor survived (OS) compared to the model-based low-risk subgroup. The area of the prognostic model under the time-dependent receiver operator characteristic (ROC) curve is 0.814 in TCGA training group and 0.729 in validation group, indicating a strong prognostic model. We also created a predictive nomogram and a web-based calculator (https://dxyjiang.shinyapps.io/RBPpredict/) based on the 4 RBPs and internal validation in the TCGA cohort, which displayed a beneficial predictive ability for HCC.
Our results provide new insights into HCC pathogenesis. The 4-RBP gene signature showed a reliable HCC prediction ability with possible applications in therapeutic decision making and personalized therapy.
RNA 结合蛋白(RBPs)的失调已在多种与肿瘤进展和发生相关的恶性肿瘤中被发现。然而,在肝细胞癌(HCC)中,RBPs 的功能尚不清楚。
从癌症基因组图谱(TCGA)数据库中提取 HCC 的 RNA 序列数据,并计算正常组织和癌组织之间的不同 RBPs。本研究通过一系列生物信息学分析,系统地研究了 RBPs 系统的表达和预测价值。
共鉴定出 330 个 RBPs,其中 208 个上调,122 个下调。四个 RBPs(MRPL54、EZH2、PPARGC1A、EIF2AK4)被定义为与预测相关的枢纽基因,并用于构建模型进行预测。进一步的研究表明,高危亚组的总生存期(OS)较模型低危亚组差。在 TCGA 训练组中,该预后模型的时间依赖性接收者操作特征(ROC)曲线下面积为 0.814,在验证组中为 0.729,表明该模型具有较强的预后能力。我们还基于 TCGA 队列中的 4 个 RBPs 构建了一个预测列线图和一个基于网络的计算器(https://dxyjiang.shinyapps.io/RBPpredict/),用于预测 HCC,显示出良好的预测能力。
我们的研究结果为 HCC 的发病机制提供了新的见解。4-RBP 基因特征显示出可靠的 HCC 预测能力,可能在治疗决策和个性化治疗中有应用价值。