Linping Gu, Yuanyuan Xu and Hong Jian*
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.
Adenocarcinoma of lung, DNA repair, prognosis, transcriptome
Department of Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, Department of Surgery Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, Department of Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030