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RNA结合蛋白在睾丸生殖细胞肿瘤患者的预后中起重要作用。

RNA-Binding Proteins Play an Important Role in the Prognosis of Patients With Testicular Germ Cell Tumor.

作者信息

Yao Liangyu, Cong Rong, Ji Chengjian, Zhou Xiang, Luan Jiaochen, Meng Xianghu, Song Ninghong

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Urology, The Affiliated Kizilsu Kirghiz Autonomous Prefecture People's Hospital of Nanjing Medical University, Artux, China.

出版信息

Front Genet. 2021 Mar 11;12:610291. doi: 10.3389/fgene.2021.610291. eCollection 2021.

DOI:10.3389/fgene.2021.610291
PMID:33777092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7990889/
Abstract

Testicular germ cell tumors (TGCTs) are common urological neoplasms in young adult males. The outcome of TGCT depends on pathologic type and tumor stage. RNA-binding proteins (RBPs) influence numerous cancers via post-transcriptional regulation. The prognostic importance of RBPs in TGCT has not been fully investigated. In this study, we set up a prognostic risk model of TGCT using six significantly differentially expressed RBPs, namely, , and . The expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression datasets. We observed by performing least absolute shrinkage and selection operator (LASSO) regression analyses that in the training cohort, the expression of six RBPs was correlated with disease-free survival in patients with TGCT. We assessed the specificity and sensitivity of 1-, 3-, 5-, and 10-year survival status prediction using receiver operating characteristic curve analysis and successfully validated using the test cohorts, the entire TCGA cohort, and Gene Expression Omnibus (GEO) datasets. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses were carried out to seek the possible signaling pathways related with risk score. We also examined the association between the model based on six RBPs and different clinical characteristics. A nomogram was established for TGCT recurrence prediction. Consensus clustering analysis was carried out to identify the clusters of TGCT with different clinical outcomes. Ultimately, external validations of the six-gene risk score were performed by using the GSE3218 and GSE10783 datasets downloaded from the GEO database. In general, our study constructed a prognostic model based on six RBPs, which could serve as independent risk factor in TGCT, especially in seminoma, and might have brilliant clinical application value.

摘要

睾丸生殖细胞肿瘤(TGCTs)是年轻成年男性中常见的泌尿系统肿瘤。TGCT的预后取决于病理类型和肿瘤分期。RNA结合蛋白(RBPs)通过转录后调控影响多种癌症。RBPs在TGCT中的预后重要性尚未得到充分研究。在本研究中,我们使用六个显著差异表达的RBPs,即 、 和 ,建立了TGCT的预后风险模型。表达谱从癌症基因组图谱(TCGA)和基因型-组织表达数据集下载。通过进行最小绝对收缩和选择算子(LASSO)回归分析,我们观察到在训练队列中,六个RBPs的表达与TGCT患者的无病生存期相关。我们使用受试者工作特征曲线分析评估了1年、3年、5年和10年生存状态预测的特异性和敏感性,并使用测试队列、整个TCGA队列和基因表达综合数据库(GEO)数据集成功进行了验证。进行了基因本体论、京都基因与基因组百科全书和基因集富集分析,以寻找与风险评分相关的可能信号通路。我们还研究了基于六个RBPs的模型与不同临床特征之间的关联。建立了TGCT复发预测的列线图。进行了一致性聚类分析,以识别具有不同临床结果的TGCT聚类。最终,通过使用从GEO数据库下载的GSE3218和GSE10783数据集对六基因风险评分进行了外部验证。总体而言,我们的研究构建了一个基于六个RBPs的预后模型,该模型可作为TGCT,尤其是精原细胞瘤的独立危险因素,可能具有出色的临床应用价值。

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