Lung Adenocarcinoma (LUAD) drastically influences human health. Tumor hypoxia and immunity impact hugely on the immunotherapeutic effect of LUAD patients. This study is aimed at exploring the prognostic markers associated with hypoxia and immunity in LUAD patients and evaluates their reliability. The relationship between hypoxia and immune-related genes and prognoses of LUAD patients was investigated by the univariate regression analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were used to reveal the enriched pathways and biological processes of prognosis-related genes. Univariate, LASSO, and multivariate Cox regression analyses were used to construct a prognostic signature and verify its independence. The reliability of the signature was evaluated by the Principal Component Analysis (PCA), the Kaplan-Meier (K-M) curve, and the receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA), tumor mutational burden (TMB), and single-sample GSEA (ssGSEA) further verified the performance of the signature. Finally, a prognostic signature for LUAD was constructed based on 7 hypoxia- and immune-related genes. According to riskScores acquired from the signature, the test set was divided into groups, where the prognosis of high-risk patients was poor. The feature genes had good reliability, and the riskScore could be used as an independent prognostic factor for LUAD patients. Meanwhile, high TMB scores and low immune scores were found in high-risk patients, and feature genes were enriched in signaling pathways such as cell cycle and p53 signaling pathway. In sum, a prognostic signature based on 7 hypoxia- and immune-related genes was constructed.

中文翻译：

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基于缺氧和免疫相关基因的肺腺癌患者预后风险评估特征

肺腺癌 (LUAD) 严重影响人类健康。肿瘤缺氧和免疫对 LUAD 患者的免疫治疗效果影响巨大。本研究旨在探索与 LUAD 患者缺氧和免疫相关的预后标志物，并评估其可靠性。通过单因素回归分析研究缺氧与免疫相关基因与LUAD患者预后的关系。基因本体论（GO）和京都基因和基因组百科全书（KEGG）方法被用来揭示预后相关基因的丰富途径和生物学过程。单变量、LASSO 和多变量 Cox 回归分析用于构建预后特征并验证其独立性。签名的可靠性通过主成分分析（PCA）评估，Kaplan-Meier (KM) 曲线和受试者工作特征 (ROC) 曲线。基因集富集分析 (GSEA)、肿瘤突变负荷 (TMB) 和单样本 GSEA (ssGSEA) 进一步验证了签名的性能。最后，基于 7 个缺氧和免疫相关基因构建了 LUAD 的预后特征。根据从签名中获得的riskScores，将测试集分组，其中高危患者的预后较差。特征基因具有良好的信度，riskScore可作为LUAD患者的独立预后因素。同时，高危患者TMB评分高、免疫评分低，特征基因在细胞周期、p53信号通路等信号通路中富集。总共，