A novel signature based on twelve programmed cell death patterns to predict the prognosis of lung adenocarcinoma.

ABSTRACT

Programmed cell death (PCD) plays a pivotal role in tumor initiation and progression. However, the prognostic value and clinical characteristics of PCD-related genes (PRGs) remain unclear. We collected and analyzed genes associated with twelve PCD patterns, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis to construct a gene signature. Our analysis identified 215 differentially expressed PRGs out of 1254 in lung adenocarcinoma (LUAD) and normal lung tissues. Subsequently, we performed univariate Cox regression analysis and identified 58 prognostic PRGs. Based on LASSO Cox regression analysis, we constructed a risk score using the expression levels of seven genes DAPK2, DDIT4, E2F2, GAPDH, MET, PIM2, and FOXF1. Patients with lower risk scores showed earlier stages of cancer, longer survival times, and better immune infiltrations and functions. Notably, we found that knockdown of DDIT4 significantly increased apoptosis and impaired the proliferation of human LUAD cell lines. Our study proposes a PRG-based prognostic signature that sheds light on the potential role of PCD-related genes in LUAD and provides valuable insights into future therapeutic strategies.