Prognostic chromatin remodeling signature stratifies survival outcomes in lung adenocarcinoma patients

Lung adenocarcinoma (LUAD) remains a major contributor to global cancer mortality, necessitating better prognostic tools. While chromatin remodeling genes (CRGs) play a pivotal role in tumorigenesis, their clinical utility in LUAD prognostication is not well defined. This study aimed to develop and validate a robust prognostic signature based on CRGs expression to stratify LUAD patients and guide clinical decision-making.

Integrative bioinformatics analysis was conducted using transcriptomic profiles and clinical data from The Cancer Genome Atlas-LUAD and Gene Expression Omnibus cohorts. Molecular subtyping was achieved through consensus clustering, followed by survival analysis. A least absolute shrinkage and selection operator Cox regression-derived prognostic model was developed, complemented by nomogram construction for clinical translation. Functional role of a key gene, GJB3, was investigated using in vitro assays.

Three CRG-defined molecular subtypes with distinct survival patterns and clinicopathological features were identified. A prognostic model of 19 genes was established, which can divide patients into two subgroups. High-risk patients demonstrated inferior overall survival and differential chemosensitivity profiles, whereas the low-risk group was associated with a lower Tumor Immune Dysfunction and Exclusion score. The risk score emerged as an independent prognostic factor across multivariate analyses. Experimental validation revealed that GJB3 knockdown substantially attenuated malignant phenotypes in LUAD cells.

This study presents a validated CRG-based prognostic model for LUAD. The nomogram offers a practical tool for individualized risk assessment and may guide immunotherapy strategy selection, supporting its potential for clinical translation in precision oncology.