Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma

Abstract

Pyroptosis is a recently identified form of programmed cell death; however, its role in lung adenocarcinoma (LUAD) remains unclear. Therefore, we set out to explore the prognostic potential of pyroptosis-related genes in LUAD. The pyroptosis-related risk score (PRRS) was developed by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression. We found that PRRS was an independent prognostic factor for LUAD. LUAD patients in the high-PRRS group showed a significantly shorter overall survival (OS) and enriched in cell proliferation-related pathways. Then pathway enrichment analyses, mutation profile, tumor microenvironment, and drug sensitivity analysis were further studied in PRRS stratified LUAD patients. Tumor purity (TP) analyses revealed that L-PRRS LUAD patients had a lower TP, and patients in L-TP + L-PRRS subgroup had the most prolonged OS. Mutation analyses suggested that the L-PRRS LUAD patients had a lower tumor mutation burden (TMB), and patients in H-TMB + L-PRRS subgroup had the most prolonged OS. Drug sensitivity analyses showed that PRRS was significantly negatively correlated with the sensitivity of cisplatin, besarotene, etc., while it was significantly positively correlated with the sensitivity of kin001-135. Eventually, a nomogram was constructed based on PRRS and clinical characters of LUAD. Overall, the pyroptosis-related signature is helpful for prognostic prediction and in guiding treatment for LUAD patients.

Keywords

• pyroptosis
• lung adenocarcinoma
• tumor microenvironment
• tumor mutation burden
• drug sensitivity