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Demystifying programmed cell death in lung adenocarcinoma: combined prognostic model construction
Yu Li1, Haitao Li1, Yuze Zhao1
1Department of Thoracic Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Translational Cancer Research
|October 29, 2025
Summary
This study developed a new prognostic model for lung adenocarcinoma (LUAD) using programmed cell death (PCD) genes, identifying necroptosis and pyroptosis as key factors. The model improves risk stratification and identifies potential therapeutic targets for LUAD patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung adenocarcinoma (LUAD) poses treatment challenges due to late diagnosis and limited options.
- The prognostic value of programmed cell death (PCD) gene signatures in LUAD requires further investigation.
Purpose of the Study:
- To develop and validate prognostic models for LUAD based on PCD-related genes.
- To improve risk stratification and identify potential therapeutic targets for LUAD patients.
Main Methods:
- Developed prognostic models using least absolute shrinkage and selection operator (LASSO) regression on 12 PCD-related genes.
- Validated models using The Cancer Genome Atlas and Gene Expression Omnibus datasets, employing machine learning and immune infiltration analyses.
Main Results:
- The combined prognostic model (CPM) showed strong predictive performance (AUC = 0.735), identifying high-risk LUAD patients with poorer survival (HR = 3.05).
- Identified 13 key prognostic genes, including PKP2 and AHSA1, and found correlations between risk scores and immune cell profiles, particularly macrophages.
Conclusions:
- Programmed cell death (PCD) plays a significant prognostic role in LUAD, with necroptosis and pyroptosis being particularly relevant.
- PKP2 and AHSA1 are identified as independent biomarkers for LUAD, offering insights for targeted therapies and personalized treatment strategies.
