Identification of immune characteristics of two lung adenocarcinoma subtypes based on immune- and pyroptosis-related genes to improve immunotherapy.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most prevalent histological subtype of lung cancer. Pyroptosis is a programmatic cell death linked to inflammation.

Methods: The data information of 541 LUAD samples and 59 normal samples were obtained from TCGA database. The analysis of differentially expressed genes (DEGs) was carried out on LUAD patients. The intersection of integrated PRGs and IRGs with DEGs yielded IPRGs. We utilized univariate Cox regression to determine IPRGs linked to overall survival (OS). Based on their expression levels, unsupervised clustering of LUAD was conducted. Patients were divided into two clusters. Analyses of immunity and drugs were performed in two clusters.

Results: One hundred and thirty-two IPRGs were linked with OS. Cluster 1 had a longer OS. Two thousand two hundred and fifty-six DEGs were detected in various subtypes. The results of immune analysis showed that most of the immune cells in cluster 2, which had a worse prognosis, had a low degree of infiltration. High Th2 cell infiltration may be related to poor prognosis in LUAD patients. Higher tumor immune dysfunction and exclusion (TIDE) and immunophenotypic scores in Cluster 1 indicated that these patients may have a better response to immunotherapy. There were significant differences in human leukocyte antigen (HLA), immune checkpoints, immunophenoscore (IPS), and TIDE scores in the two subtypes. The mutation frequencies of the top 10 genes in cluster 2 were higher than those in cluster 1. Different subtypes also had distinct sensitivities to different drugs.

Conclusion: IPRGs can be utilized for LUAD subtyping. Different subtypes have varied immune landscapes and immunotherapy responses.