Abstract

Accumulating evidence indicates that immunotherapy helped to improve the survival and quality-of-life of patients with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC) besides chemotherapy and gene targeting treatment. This study aimed to develop immune-related gene signatures in LUAD and LUSC subtypes, respectively. LUAD and LUSC samples were divided into high- and low-abundance groups of immune cell infiltration (Immunity_H and Immunity_L) based on the abundance of immune cell infiltrations. The distribution of immune cells was significantly different between the high- and low-immunity subtypes in LUAD and LUSC samples. The differentially expressed genes (DEGs) between those two groups in LUAD and LUSC contain some key immune-related genes, such as PDL1, PD1, CTLA-4, and HLA families. The DEGs were enriched in multiple immune-related pathways. Furthermore, the seven-immune-related-gene-signature (CD1B, CHRNA6, CLEC12B, CLEC17A, CLNK, INHA, and SLC14A2) prognostic model-based high- and low-risk groups were significantly associated with LUAD overall survival and clinical characteristics. The eight-immune-related-gene-signature (C4BPB, FCAMR, GRAPL, MAP1LC3C, MGC2889, TRIM55, UGT1A1, and VIPR2) prognostic model-based high- and low-risk groups were significantly associated with LUSC overall survival and clinical characteristics. The prognostic models were tested as good ones by receiver operating characteristic, principal component analysis, univariate and multivariate analysis, and nomogram. The verifications of these two immune-related-gene-signature prognostic models showed consistency in the train and test cohorts of LUAD and LUSC. In addition, patients with LUAD in the low-risk group responded better to immunotherapy than those in the high-risk group. This study revealed two reliable immune-related-gene-signature models that were significantly associated with prognosis and tumor microenvironment cell infiltration in LUAD and LUSC, respectively. Evaluation of the integrated characterization of multiple immune-related genes and pathways could help to predict the response to immunotherapy and monitor immunotherapy strategies.

Highlights

  • Lung cancer is the most common malignant tumor worldwide, and its incidence and mortality have been increasing year by year among men and women, which has caused a serious burden on patients and society

  • This study revealed two reliable gene signature models that were significantly associated with prognosis and tumor microenvironment (TME) cell infiltration in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), respectively, which can promote individualized treatment and offer potential new targets of immunotherapy

  • The abundance of each TME cell infiltration was calculated by single-sample Gene Set Enrichment Analysis (ssGSEA) with gene expression data in LUAD and LUSC (Supplementary Tables S5 and S6), including the immune cell information of central memory (Tcm), activated T cells, effector memory (Tem) CD4+ and CD8+ T cells, T helper 1 (Th1) cells, gamma delta T (Tgd) cells, Th17 cells, Th2 cells, follicular helper T cells (Tfh), regulatory T cells (Treg), and activated, immature, and memory B cells, as well as innate immunity-related cell types

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Summary

Introduction

Lung cancer is the most common malignant tumor worldwide, and its incidence and mortality have been increasing year by year among men and women, which has caused a serious burden on patients and society. LUAD has a sensitive mutation-targeted treatment plan compared to LUSC, but a patient’s prognosis with advanced NSCLC is still very poor and the 5-year survival rate might be

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