BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent subtype of lung cancer. The prognostic signature could be reliable to stratify LUAD patients according to risk, which helps the management of the systematic treatments. In this study, a systematic and reliable immune signature was performed to estimate the prognostic stratification in LUAD. METHODS The profiles of immune-related genes for patients with LUAD were used as one TCGA training set: n = 494, other validation set 1: n = 226 and validation set 2: n = 398. Univariate Cox survival analysis was used to identify the candidate immune-related genes from each cohort. Then, the immune signature was developed and validated in the training and validation sets. RESULTS In this study, functional analysis showed that immune-related genes involved in immune regulation and MAPK signaling pathway. A prognostic signature based on 10 immune-related genes was established in the training set and patients were divided into high-risk and low-risk groups. Our 10 immune-related gene signature was significantly related to worse survival, especially during early-stage tumors. Further stratification analyses revealed that this 10 immune-related gene signature was still an effective tool for predicting prognosis in smoking or nonsmoking patients, patients with KRAS mutation or KRAS wild-type, and patients with EGFR mutation or EGFR wild-type. Our signature was negatively correlated with B cell, CD4+ T cell, CD8+ T cell, neutrophil, dendritic cell (DC), and macrophage immune infiltration, and immune checkpoint molecules PD-1 and CTLA-4 (P < 0.05). CONCLUSIONS These findings suggested that our signature was a promising biomarker for prognosis prediction and can facilitate the management of immunotherapy in LUAD.

中文翻译：

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肺腺癌生存预测和免疫检查点分子的新免疫特征。

背景技术肺腺癌（LUAD）是最常见的肺癌亚型。预后签名可以可靠地根据风险将LUAD患者分层，这有助于系统治疗的管理。在这项研究中，进行了系统和可靠的免疫标记，以评估LUAD的预后分层。方法将LUAD患者的免疫相关基因谱作为一个TCGA训练集：n = 494，其他验证集1：n = 226和验证集2：n =398。单变量Cox生存分析用于确定每个队列的候选免疫相关基因。然后，在训练和验证集中开发并验证了免疫标记。结果在这项研究中，功能分析表明，免疫相关基因参与了免疫调节和MAPK信号通路。在训练集中建立了基于10个免疫相关基因的预后标志，并将患者分为高危和低危组。我们的10个与免疫相关的基因标记与存活率下降显着相关，尤其是在早期肿瘤期间。进一步的分层分析显示，这10个与免疫相关的基因标记仍然是预测吸烟或不吸烟患者，具有KRAS突变或KRAS野生型的患者以及具有EGFR突变或EGFR野生型的患者预后的有效工具。我们的签名与B细胞，CD4 + T细胞，CD8 + T细胞，中性粒细胞，树突状细胞（DC）和巨噬细胞免疫浸润以及免疫检查点分子PD-1和CTLA-4呈负相关（P < 0.05）。结论这些发现表明我们的签名是用于预后预测的有前途的生物标志物，可以促进LUAD免疫治疗的管理。