Abstract
BackgroundLung 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.MethodsThe 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.ResultsA 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.ConclusionsThis 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.
Highlights
Lung cancer has become the most common cancer type and caused the most cancer deaths
The RNA sequencing (RNA-seq) data of 500 Lung adenocarcinoma (LUAD) patients were collected from the The Cancer Genome Atlas (TCGA) database and used as the training set, which were downloaded from University of California Santa Cruz (UCSC) Genome Browser
The 144 immune related genes underwent the Cox proportional hazards regression with tenfold cross-validation to generate the best gene model
Summary
Lung cancer has become the most common cancer type and caused the most cancer deaths. Song et al J Transl Med (2019) 17:70 kinase (ALK) gene rearrangements are other common oncogenes which are somatically activated for the targeted therapies of LUAD [6]. A large amount of advanced LUAD patients do not have targetable mutations For these patients, antibodies against immune checkpoints like programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) demonstrate established treatment activity and safety [7, 8]. Antibodies against immune checkpoints like programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) demonstrate established treatment activity and safety [7, 8] This highlights the importance of tumor immune microenvironment (TIM) on the clinical outcomes of LUAD patients
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