机构：[1]Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, The Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,外科中心胸外科中心四川省人民医院四川省肿瘤医院胸外科[2]Department of Thoracic Surgery, Guizhou Provincial People’s Hospital, Guiyang, China,[3]Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China,昆明医科大学附属第一医院[4]Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, China四川大学华西医院
Objective: To conduct a robust prognostic gene expression signature and characterize molecular subtypes with distinct clinical characteristics for lung adenocarcinoma (LUAD). Methods: Based on DNA repair genes from the GSEA database, a prognostic signature was conducted in the TCGA-LUAD training set via univariate and multivariate cox regression analysis. Its prediction power was validated by overall survival analysis, relative operating characteristic (ROC) curves and stratification analysis in the GSE72094 verification set. Involved pathways in the high- and low-risk groups were analyzed by GSEA. A nomogram was built based on the signature and clinical features and its performance was assessed by calibration plots. LUAD samples were clustered via the ConsensusClusterPlus package. The differences in clinical outcomes, single nucleotide polymorphism (SNP) and sensitivity to chemotherapy drugs between molecular subtypes were analyzed. Results: A 13-DNA repair gene-signature was constructed for LUAD prognosis. Following validation, it can robustly and independently predict patients' clinical outcomes. The GSEA results exhibited the differences in pathways between high- and low- risk groups. A nomogram combining the signature and stage could accurately predict 1-, 3-, and 5-year survival probability. Two distinct molecular subtypes were characterized based on DNA repair genes. Patients in the Cluster 2 exhibited a worse prognosis and were more sensitive to common chemotherapy than those in the Cluster 1. Conclusion:This study proposed a 13-DNA repair gene-signature as a prognostic factor for LUAD patients, which can independently predict clinical outcomes by complement of the stage. Moreover, we characterized two LUAD subtypes with distinct clinical outcomes, somatic gene mutations, and drug sensitivity in cancer based on DNA repair genes.
基金：
Sichuan Science and Technology Program (CN) [2019JDRC0068, 2019YFG0517]; Research Project of Sichuan Provincial Health Commission [19PJ254]; Yunnan Province Health and Family Planning Commission Medical Reserve Talents Plan [H-2017-013]; 2018CSCO-Qilu Cancer Research Fund [Y-Q201802-011]
第一作者机构：[1]Department of Thoracic Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, The Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China,
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推荐引用方式(GB/T 7714)：
Hu Bin,Liu Di,Liu Yinqiang,et al.DNA Repair-Based Gene Expression Signature and Distinct Molecular Subtypes for Prediction of Clinical Outcomes in Lung Adenocarcinoma[J].FRONTIERS IN MEDICINE.2020,7:doi:10.3389/fmed.2020.615981.
APA：
Hu, Bin,Liu, Di,Liu, Yinqiang&Li, Zhixi.(2020).DNA Repair-Based Gene Expression Signature and Distinct Molecular Subtypes for Prediction of Clinical Outcomes in Lung Adenocarcinoma.FRONTIERS IN MEDICINE,7,
MLA：
Hu, Bin,et al."DNA Repair-Based Gene Expression Signature and Distinct Molecular Subtypes for Prediction of Clinical Outcomes in Lung Adenocarcinoma".FRONTIERS IN MEDICINE 7.(2020)
