Identification of an inflammatory response signature associated with prognostic stratification and drug sensitivity in lung adenocarcinoma

Abstract

Increasing evidence has confirmed the close connection between inflammatory response and tumorigenesis. However, the relationship between inflammatory response genes (IRGs) and the prognosis of lung adenocarcinoma (LUAD) as well as the response to drug therapy remains poorly investigated. Here, we comprehensively analyzed IRGs RNA expression profiling and clinical features of over 2000 LUAD patients from 12 public datasets. The Cox regression method and LASSO analysis were combined to develop a novel IRG signature for risk stratification and drug efficacy prediction in LUAD patients. Enriched pathways, tumor microenvironment (TME), genomic and somatic mutation landscape in different subgroups were evaluated and compared with each other. This established IRG signature including 11 IRGs (ADM, GPC3, IL7R, NMI, NMURI, PSEN1, PTPRE, PVR, SEMA4D, SERPINE1, SPHK1), could well categorize patients into significantly different prognostic subgroups, and have better predictive in independently assessing survival as compared to a single clinical factor. High IRG scores (IRGS) patients might benefit more from immunotherapy and chemotherapy. Comprehensive analysis uncovered significant differences in enriched pathways, TME, genomic and somatic mutation landscape between the two subgroups. Additionally, integrating the IRGS and TNM stage, a reliable prognostic nomogram was developed to optimize survival prediction, and validated in an independent external dataset for clinical application. Take together, the proposed IRG signature in this study is a promising biomarker for risk stratification and drug efficacy prediction in LUAD patients. This study may be meaningful for explaining the responses of clinical therapeutic drugs and providing new strategies for administrating sufferer of LUAD.