Background. There is plenty of evidence showing that immune-related genes (IRGs) and epigenetic modifications play important roles in the biological process of cancer. The purpose of this study is to establish novel IRG prognostic markers by integrating mRNA expression and methylation in lung adenocarcinoma (LUAD). Methods and Results. The transcriptome profiling data and the RNA-seq data of LUAD with the corresponding clinical information of 543 LUAD cases were downloaded from The Cancer Genome Atlas (TCGA) database, which were analyzed by univariate Cox proportional regression and multivariate Cox proportional regression to develop an independent prognostic signature. On the basis of this signature, we could divide LUAD patients into the high-risk, medium-risk, and low-risk groups. Further survival analyses demonstrated that high-risk patients had significantly shorter overall survival (OS) than low-risk patients. The signature, which contains 8 IRGs (S100A16, FGF2, IGKV4-1, CX3CR1, INHA, ANGPTL4, TNFRSF11A, and VIPR1), was also validated by data from the Gene Expression Omnibus (GEO) database. We also conducted analyses of methylation levels of the relevant IRGs and their CpG sites. Meanwhile, their associations with prognosis were examined and validated by the GEO database, revealing that the methylation levels of INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 may be used as the potential regulators for the treatment of LUAD. Conclusion. Collectively, INHA, S100A16, the CpG site cg23851011, and the CpG site cg06552037 are promising biomarkers for monitoring the outcomes of LUAD.

中文翻译：

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通过整合肺腺癌中的 mRNA 表达和甲基化来鉴定预后免疫相关基因。

背景。大量证据表明，免疫相关基因 (IRG) 和表观遗传修饰在癌症的生物学过程中发挥着重要作用。本研究的目的是通过整合肺腺癌 (LUAD) 中的 mRNA 表达和甲基化来建立新的 IRG 预后标志物。方法和结果. 从癌症基因组图谱（TCGA）数据库下载 LUAD 的转录组分析数据和 RNA-seq 数据以及 543 例 LUAD 病例的相应临床信息，通过单变量 Cox 比例回归和多变量 Cox 比例回归进行分析，以开发独立的预后签名。根据这一特征，我们可以将 LUAD 患者分为高危、中危和低危组。进一步的生存分析表明，高风险患者的总生存期 (OS) 明显短于低风险患者。该签名包含 8 个 IRG（S100A16、FGF2、IGKV4-1、CX3CR1、INHA、ANGPTL4、TNFRSF11A 和 VIPR1），还通过来自 Gene Expression Omnibus (GEO) 数据库的数据进行了验证。我们还对相关 IRG 及其 CpG 位点的甲基化水平进行了分析。同时，通过 GEO 数据库检查和验证了它们与预后的关联，揭示了 INHA、S100A16、CpG 位点 cg23851011 和 CpG 位点 cg06552037 的甲基化水平可用作治疗 LUAD 的潜在调节因子。结论。总之，INHA、S100A16、CpG 位点 cg23851011 和 CpG 位点 cg06552037 是用于监测 LUAD 结果的有前途的生物标志物。