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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

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

Author(s): Linping Gu, Yuanyuan Xu and Hong Jian*

Volume 25, Issue 9, 2022

Published on: 11 January, 2022

Page: [1437 - 1449] Pages: 13

DOI: 10.2174/1386207324666210716104714

Price: $65

Abstract

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 DDRrelated 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. Cluster2 had the best prognosis, while cluster3 had the worst. Compared to cluster2, clusters 1 and 3 consisted of more stage3 - 4, T2-T4, male, and older samples. The feature genes of clusters1, 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.

Keywords: Adenocarcinoma of lung, DNA repair, prognosis, transcriptome, DDR-related gene, malignancy.

Graphical Abstract

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