Department of Blood Transfusion, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Department of Urology, Shenzhen Longhua District Central Hospital, Shenzhen, China.
Front Immunol. 2022 Aug 18;13:964919. doi: 10.3389/fimmu.2022.964919. eCollection 2022.
Oxidative stress (OS) response is crucial in oncogenesis and progression of tumor. But the potential prognostic importance of OS-related genes (OSRGs) in stomach adenocarcinoma (STAD) lacked comprehensive study. STAD clinical information and transcriptome data were retrieved from the Gene Expression Omnibus and The Cancer Genome Atlas databases. The prognostic OSRGs were filtered the univariate Cox analysis and OSRG-based molecular subtypes of STAD were developed using consensus clustering. Weighted gene co-expression network analysis (WGCNA) was subsequently conducted to filter molecular subtype-associated gene modules. The prognosis-related genes were screened univariate and least absolute shrinkage and selection operator Cox regression analysis were used to construct a prognostic risk signature. Finally, a decision tree model and nomogram were developed by integrating risk signature and clinicopathological characteristics to analyze individual STAD patient's survival. Four OSRG-based molecular subtypes with significant diversity were developed based on 36 prognostic OSRGs for STAD, and an OSRGs-based subtype-specific risk signature with eight genes for prognostic prediction of STAD was built. Survival analysis revealed a strong prognostic performance of the risk signature exhibited in predicting STAD survival. There were significant differences in mutation patterns, chemotherapy sensitivity, clinicopathological characteristics, response to immunotherapy, biological functions, immune microenvironment, immune cell infiltration among different molecular subtypes and risk groups. The risk score and age were verified as independent risk factors for STAD, and a nomogram integrating risk score and age was established, which showed superior predictive performance for STAD prognosis. We developed an OSRG-based molecular subtype and identified a novel risk signature for prognosis prediction, providing a useful tool to facilitate individual treatment for patients with STAD.
氧化应激（OS）反应在肿瘤的发生和发展中至关重要。但是，OS 相关基因（OSRG）在胃腺癌（STAD）中的潜在预后意义缺乏全面研究。从基因表达综合数据库和癌症基因组图谱数据库中检索了 STAD 的临床信息和转录组数据。通过单因素 Cox 分析筛选预后 OSRG，并使用共识聚类方法构建基于 OSRG 的 STAD 分子亚型。随后进行加权基因共表达网络分析（WGCNA）筛选与分子亚型相关的基因模块。使用单因素和最小绝对收缩和选择算子 Cox 回归分析筛选预后相关基因，构建预后风险特征。最后，通过整合风险特征和临床病理特征，构建决策树模型和诺莫图，分析个体 STAD 患者的生存情况。基于 36 个 STAD 预后 OSRG 构建了 4 个基于 OSRG 的分子亚型，构建了一个基于 OSRGs 的具有 8 个基因的预测 STAD 预后的特定风险特征。生存分析显示，该风险特征在预测 STAD 生存方面具有很强的预后性能。不同分子亚型和风险组之间存在明显的突变模式、化疗敏感性、临床病理特征、免疫治疗反应、生物学功能、免疫微环境和免疫细胞浸润差异。风险评分和年龄被验证为 STAD 的独立危险因素，建立了一个整合风险评分和年龄的诺莫图，对 STAD 预后具有更好的预测性能。我们开发了基于 OSRG 的分子亚型，并确定了一个新的用于预后预测的风险特征，为 STAD 患者的个体化治疗提供了有用的工具。
