Identification of an immune-related genes signature in lung adenocarcinoma to predict survival and response to immune checkpoint inhibitors
Research Square (Research Square)(2022)
Abstract
Abstract Background Although advances in immune checkpoint inhibitor (ICI) research have provided a new treatment approach for lung adenocarcinoma (LUAD) patients, their survival is still unsatisfactory, and there are issues in the era of response prediction to immunotherapy. We aimed to develop a prognostic model based on immune-related genes (IRGs) to predict the overall survival (OS) as well as response to ICIs in LUAD patients. Methods Using bioinformatics methods, a prognostic signature was constructed and its predictive ability was validated both in the internal and external datasets (GSE68465). We also explored the tumor-infiltrating immune cells, mutation profiles, and immunophenoscore (IPS) in the low-and high-risk groups. Results A prognostic signature based on 9-IRGs, including BIRC5, CBLC, S100P, SHC3, ANOS1, VIPR1, LGR4, PGC, and IGKV4.1 was developed. According to multivariate analysis, the 9-IRG signature provided an independent prognostic factor for OS in LUAD patients. The low-risk group had better OS, and the tumor mutation burden (TMB) was significantly lower in this group. Moreover, the risk scores were negatively associated with the tumor-infiltrating immune cells, like CD8+ T cells, macrophages, dendritic cells, and NK cells. In addition, the IPS were significantly higher in the low-risk group as they had higher gene expression of immune checkpoints, suggesting that ICIs could be a promising treatment option for low-risk LUAD patients. Conclusion Our 9-IRGs prognostic signature could be useful in predicting the survival of LUAD patients and their response to ICIs; hoping this model paves the way for better stratification and management of patients in clinical practice.
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Key words
lung adenocarcinoma,genes signature,immune-related
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