Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong-An Road, Shanghai, 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong-An Road, Shanghai, 200032, China.
J Transl Med. 2019 Mar 4;17(1):70. doi: 10.1186/s12967-019-1824-4.
Lung cancer has become the most common cancer type and caused the most cancer deaths. Lung adenocarcinoma (LUAD) is one of the major type of lung cancer. This study aimed to establish a signature based on immune related genes that can predict patients' OS for LUAD.
The expression data of 976 LUAD patients from The Cancer Genome Atlas database (training set) and the Gene Expression Omnibus database (four testing sets) and 1534 immune related genes from the ImmPort database were used for generation and validation of the signature. The glmnet Cox proportional hazards model was used to find the best gene model and construct the signature. To assess the independently prognostic ability of the signature, the Kaplan-Meier survival analysis and Cox's proportional hazards model were performed.
A gene model consisting of 30 immune related genes with the highest frequency after 1000 iterations was used as our signature. The signature demonstrated robust prognostic ability in both training set and testing set and could serve as an independent predictor for LUAD patients in all datasets except GSE31210. Besides, the signature could predict the overall survival (OS) of LUAD patients in different subgroups. And this signature was strongly associated with important clinicopathological factors like recurrence and TNM stage. More importantly, patients with high risk score presented high tumor mutation burden.
This signature could predict prognosis and reflect the tumor immune microenvironment of LUAD patients, which can promote individualized treatment and provide potential novel targets for immunotherapy.
肺癌已成为最常见的癌症类型,也是导致癌症死亡人数最多的癌症。肺腺癌 (LUAD) 是肺癌的主要类型之一。本研究旨在建立一个基于免疫相关基因的signature,用于预测 LUAD 患者的总生存期 (OS)。
从癌症基因组图谱数据库 (训练集) 和基因表达 Omnibus 数据库 (四个测试集) 中获取 976 例 LUAD 患者的表达数据,以及从 ImmPort 数据库中获取 1534 个免疫相关基因,用于 signature 的生成和验证。使用 glmnet Cox 比例风险模型寻找最佳基因模型并构建 signature。通过 Kaplan-Meier 生存分析和 Cox 比例风险模型评估 signature 的独立预后能力。
使用经过 1000 次迭代后频率最高的 30 个免疫相关基因构建的基因模型作为我们的 signature。该 signature 在训练集和测试集中均具有稳健的预后能力,并且可以作为所有数据集(除 GSE31210 外)中 LUAD 患者的独立预测因子。此外,该 signature 可以预测不同亚组 LUAD 患者的总生存期 (OS)。并且该 signature 与复发和 TNM 分期等重要临床病理因素密切相关。更重要的是,高风险评分的患者具有较高的肿瘤突变负担。
该 signature 可以预测 LUAD 患者的预后并反映肿瘤免疫微环境,有助于个体化治疗,并为免疫治疗提供潜在的新靶点。