An Inflammatory Response-Related Gene Signature Can Predict the Prognosis and Impact the Immune Status of Lung Adenocarcinoma

SIMPLE SUMMARY: Lung adenocarcinoma (LUAD) is a highly prevalent and deadly global malignancy with an annual increase in its incidence. The association of inflammation with tumor genesis and development has been of interest in recent years. However, the association of inflammatory response-related genes (IRGs) with LUAD remains unclear. In this study, we verified an inflammatory response-related gene signature to establish an independent relationship with overall survival, whose importance was in functional analysis, tumor microenvironment, drug sensitivity, and prognosis prediction in LUAD. Therefore, our study revealed the role of IRGs in tumorigenesis, especially in drug resistance, immune response, and tumor microenvironment, which is crucial in developing individualized tumor treatment. ABSTRACT: Lung adenocarcinoma (LUAD) accounts for a cancer with high heterogeneity and poor prognostic outcome. Nonetheless, it is still unknown about the relation between inflammatory response-related genes (IRGs) and LUAD. This study used LASSO-Cox regression for establishing the multigene prognostic signature based on TCGA and the GSE31210 cohorts. In addition, gene set enrichment analysis (GSEA) was performed for GO and KEGG analyses. By contrast, single-sample GSEA (ssGSEA) investigated immune cell infiltration scores as well as the immune pathway activity. We also conducted qRT-PCR and IHC to evaluate prognostic gene expression at protein and mRNA levels within LUAD and adjacent healthy samples. As a result, a novel prognostic signature involving 10 IRGs was identified. Furthermore, the signature has been validated as being important in functional analysis, TME, drug sensitivity, and prognosis prediction in LUAD. Moreover, prognostic genes showed significant expression at protein and mRNA levels in LUAD compared with normal samples. The signature involving 10 IRGs could potentially predict LUAD prognosis.