Identification of key genes in Wilms tumor based on high-throughput RNA sequencing and their impacts on prognosis and immune responses
10.12122/j.issn.1673-4254.2024.04.15
- VernacularTitle:基于高通量RNA测序分析Wilms瘤中关键基因对预后及免疫应答的影响
- Author:
Zhiqiang GAO
1
;
Jie LIN
;
Peng HONG
;
Zaihong HU
;
Junjun DONG
;
Qinlin SHI
;
Xiaomao TIAN
;
Feng LIU
;
Guanghui WEI
Author Information
1. 重庆医科大学附属儿童医院泌尿外科//国家儿童健康与疾病临床医学研究中心//儿童发育疾病研究教育部重点实验室//结构性出生缺陷与器官修复重建重庆市重点实验室,重庆 400014
- Keywords:
Wilms tumor;
nephroblastoma;
RNA sequencing;
prognostic markers;
immune microenvironment;
prognostic model
- From:
Journal of Southern Medical University
2024;44(4):727-738
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify the key genes differentially expressed in Wilms tumor and analyze their potential impacts on prognosis and immune responses of the patients. Methods High-throughput RNA sequencing was used to identify the differentially expressed mRNAs in clinical samples of Wilms tumor and paired normal tissues, and their biological functions were analyzed using GO, KEGG and GSEA enrichment analyses. The hub genes were identified using STRING database, based on which a prognostic model was constructed using LASSO regression. The mutations of the key hub genes were analyzed and their impacts on immunotherapy efficacy was predicted using the cBioPortal platform. RT-qPCR was used to verify the differential expressions of the key hub genes in Wilms tumor. Results Of the 1612 differentially expressed genes identified in Wilms tumor, 1030 were up-regulated and 582 were down-regulated, involving mainly cell cycle processes and immune responses. Ten hub genes were identified, among which 4 genes (TP53, MED1, CCNB1 and EGF) were closely related to the survival of children with Wilms tumor. A 3-gene prognostic signature was constructed through LASSO regression analysis, and the patients stratified into with high- and low-risk groups based on this signature had significantly different survival outcomes (HR=1.814, log-rank P=0.002). The AUCs of the 3-, 5-and 7-year survival ROC curves of this model were all greater than 0.7. The overall mutations in the key hub genes or the individual mutations in TP53/CCNB1 were strongly correlated with a lower survival rates, and a high TP53 expression was correlated with a poor immunotherapy efficacy. RT-qPCR confirmed that the key hub genes had significant differential expressions in Wilms tumor tissues and cells. Conclusion TP53 gene plays an important role in the Wilms tumor and may potentially serve as a new immunotherapeutic biomarker as well as a therapeutic target.
