Identification and validation of mitochondrial transport and glycolysis-associated prognostic and therapeutic target for lung adenocarcinoma patients

Le résumé fourni par la source

Background: Lung adenocarcinoma (LUAD) remains a leading cause of cancer mortality, with metabolic reprogramming, particularly dysregulated mitochondrial transport and glycolysis (MG), emerging as a hallmark of its progression. Despite the recognized importance of these pathways, an integrated, clinically actionable model that combines them for patient stratification and therapeutic targeting is lacking. Objective: This study aims to decode integrated MG-associated molecular patterns in the progression of LUAD, providing novel clinical actionable target for LUAD patients. Methods: GSVA and WGCNA were applied to an integrated GEO cohort to identify MG-associated genes. LASSO-Cox and multivariable Cox analyses were used to construct and validate a prognostic model and prioritize CCNA2 as a prognostic candidate. Single-cell, spatial, cell-based, drug-sensitivity, and xenograft analyses were used for validation. Results: The MG-associated signature stratified overall survival, and CCNA2 was enriched in malignant cells. CCNA2 knockdown reduced A549 proliferation, wound closure, and invasion. GSCA analysis identified BHG712, IPA-3, and KIN001-260 as candidate compounds, and IPA-3 produced the largest reduction in xenograft tumor burden. Conclusion: The integrated analyses identify an MG-associated prognostic framework and prioritize CCNA2 for further validation in LUAD.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.