Comprehensive Analysis of Programmed Cell Death Signature in the Prognosis, Tumor Microenvironment and Drug Sensitivity in Lung Adenocarcinoma

Abstract

Programmed cell death (PCD) is a process that regulates the homeostasis of cells in the body, and it plays an important role in tumor immunity. However, the expression profile and clinical characteristics of PCD-related genes remain unclear. In this study, we comprehensively analysed the PCD genes with the tumor microenvironment (TME), drug sensitivity, immunothearapy response, and evaluated their prognostic value through systematic bioinformatics methods.We identified 125 PCD-related regulatory factors, which were expressed differently in lung adenocarcinoma (LUAD) and normal lung tissues. 32 PCD related prognostic genes associated with LUAD were identified by univariate Cox analysis. 23 PCD-related gene signature was constructed, and all LUAD patients in the Cancer Genome Atlas (TCGA) dataset were stratified as low-risk or high-risk groups according to the risk score. This signature had a powerful prognostic value, which was validated in three independent data sets and clinical subtypes. Additionally, it has unique properties in TME. Further analysis showed that different risk groups have different immune cell infiltration, immune inflammation profile, immune pathways, and immune subtypes. In addition, the low-risk group had a better immunotherapy response with higher levels of multiple immune checkpoints and lower Tumor immune dysfunction and exclusion (TIDE) score, while the high-risk group was sensitive to multiple chemotherapeutic drugs because of its lower IC50. In short, this is the first model to predict the prognosis and immunological status of LUAD patients based on PCD-related genes. It may be used as a predictor of immunotherapy response to achieve customized treatment of LUAD.