Wang Guoguang, Zhan Tian, Li Fan, Shen Jian, Gao Xiang, Xu Lei, Li Yuan, Zhang Jianping
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
J Cancer. 2021 Apr 12;12(11):3344-3353. doi: 10.7150/jca.49658. eCollection 2021.
Gastric cancer represents a major public health problem. Owing to the great heterogeneity of GC, conventional clinical characteristics are limited in the accurate prediction of individual outcomes and survival. This study aimed to establish a robust gene signature to predict the prognosis of GC based on multiple datasets. Initially, we downloaded raw data from four independent datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and performed univariate Cox proportional hazards regression analysis to identify prognostic genes associated with overall survival (OS) from each dataset. Thirteen common genes from four datasets were screened as candidate prognostic signatures. Then, a risk score model was developed based on this 13‑gene signature and validated by four independent datasets and the entire cohort. Patients with a high-risk score had poorer OS and recurrence-free survival (RFS). Multivariate regression and stratified analysis revealed that the 13-gene signature was not only an independent predictive factor but also associated with recurrence when adjusting for other clinical factors. Furthermore, in the high-risk group, gene set enrichment analysis (GSEA) showed that the mTOR signaling pathway and MAPK signaling pathway were significantly enriched. The present study provided a robust and reliable gene signature for prognostic prediction of both OS and RFS of patients with GC, which may be useful for delivering individualized management of patients.
胃癌是一个重大的公共卫生问题。由于胃癌具有高度异质性,传统的临床特征在准确预测个体预后和生存方面存在局限性。本研究旨在基于多个数据集建立一个强大的基因特征以预测胃癌的预后。首先,我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)的四个独立数据集中下载原始数据,并进行单变量Cox比例风险回归分析,以从每个数据集中识别与总生存期(OS)相关的预后基因。从四个数据集中筛选出13个共同基因作为候选预后特征。然后,基于这13个基因特征建立了一个风险评分模型,并通过四个独立数据集和整个队列进行验证。高风险评分的患者总生存期和无复发生存期(RFS)较差。多变量回归和分层分析表明,在调整其他临床因素时,这13个基因特征不仅是一个独立的预测因素,而且与复发相关。此外,在高风险组中,基因集富集分析(GSEA)显示mTOR信号通路和MAPK信号通路显著富集。本研究为胃癌患者的总生存期和无复发生存期的预后预测提供了一个强大且可靠的基因特征,这可能有助于为患者提供个体化管理。