Identification of a 15 DNA Damage Repair-Related Gene Signature as a Prognostic Predictor for Lung Adenocarcinoma.

Background Lung Adenocarcinoma (LUAD) is a common malignancy with a poor prognosis due to the lack of predictive markers. DNA Damage Repair (DDR)-related genes are closely related to cancer progression and treatment. Introduction To identify a reliable DDR-related gene signature as an independent predictor of LUAD. Methods DDR-related genes were obtained using combined analysis of TCGA-LUAD data and literature information, followed by the identification of DDR-related prognostic genes. The DDR-related molecular subtypes were then screened, followed by Kaplan-Meier analysis, feature gene identification, and pathway enrichment analysis of each subtype. Moreover, Cox and LASSO regression analyses were performed for the feature genes of each subtype to construct a prognostic model. The clinical utility of the prognostic model was confirmed using the validation dataset GSE72094 and nomogram analysis. Results Eight DDR-related prognostic genes were identified from 31 DDR-related genes. Using consensus cluster analysis, three molecular subtypes were screened. Cluster 2 had the best prognosis, while cluster 3 had the worst. Compared to cluster 2, clusters 1 and 3 consisted of more stage 3 - 4, T2-T4, male, and older samples. The feature genes of clusters 1, 2, and 3 were mainly enriched in the cell cycle, arachidonic acid metabolism, and ribosomes. Furthermore, a 15-feature gene signature was identified for improving the prognosis of LUAD patients. Conclusion The 15 DDR-related feature gene signature is an independent and powerful prognostic biomarker for LUAD that may improve risk classification and provide supplementary information for a more accurate evaluation and personalized treatment.