Independent validation of early-stage non-small cell lung cancer prognostic scores incorporating epigenetic and transcriptional biomarkers with gene-gene interactions and main effects
| العنوان: | Independent validation of early-stage non-small cell lung cancer prognostic scores incorporating epigenetic and transcriptional biomarkers with gene-gene interactions and main effects |
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| المؤلفون: | Jieyu He, Yongyue Wei, Dongfang You, David C. Christiani, Manel Esteller, Weiwei Duan, Liya Liu, Maria Moksnes Bjaanæs, Li Su, Ruyang Zhang, Maria Planck, Rui Wang, Åslaug Helland, Yi Li, Chao Chen, Jiajin Chen, Feng Chen, Xin Chen, Johan Staaf, Thomas Fleischer, Sipeng Shen, Lijuan Lin, Liangmin Wei, Ying Zhu, Yichen Guo, Hui Huang, Andrea Shafer, Anna Karlsson, Xuesi Dong, Linjing Lai |
| المصدر: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Chest |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Oncology, Male, Lung Neoplasms, Critical Care and Intensive Care Medicine, Epigenesis, Genetic, AUC, area under the receiver operating characteristic curve, SIS, sure independence screening, 0302 clinical medicine, Non-small cell lung cancer, Carcinoma, Non-Small-Cell Lung, 030212 general & internal medicine, GEO, Gene Expression Omnibus, KEGG, Kyoto Encyclopedia of Genes and Genomes, Original Research, education.field_of_study, Hazard ratio, Middle Aged, early stage, LUAD, lung adenocarcinoma, Prognosis, prognostic score, Prognostic score, DNA methylation, Disease Progression, Biomarker (medicine), Female, Cardiology and Cardiovascular Medicine, Cindex, concordance index, G×G, gene-gene interactions, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Interaction, TCGA, the Cancer Genome Atlas, Population, interaction, 03 medical and health sciences, Internal medicine, NSCLC, non-small cell lung cancer, medicine, ISIS, iterative sure independence screening, Biomarkers, Tumor, Humans, Epigenetics, KEGG, education, Lung cancer, non-small cell lung cancer, Aged, Neoplasm Staging, Receiver operating characteristic, MGH, Massachusetts General Hospital, business.industry, Early stage, CPTAC, Clinical Proteomic Tumor Analysis Consortium, LUSC, lung squamous cell carcinoma, Epistasis, Genetic, DNA Methylation, medicine.disease, Multiomics, HR, hazard ratio, Survival Analysis, ROC, receiver operating characteristic, QC, quality control, 030228 respiratory system, business, multiomics |
| الوصف: | Background DNA methylation and gene expression are promising biomarkers of various cancers, including non-small cell lung cancer (NSCLC). Besides the main effects of biomarkers, the progression of complex diseases is also influenced by gene-gene (G×G) interactions. Research Question Would screening the functional capacity of biomarkers on the basis of main effects or interactions, using multiomics data, improve the accuracy of cancer prognosis? Study Design and Methods Biomarker screening and model validation were used to construct and validate a prognostic prediction model. NSCLC prognosis-associated biomarkers were identified on the basis of either their main effects or interactions with two types of omics data. A prognostic score incorporating epigenetic and transcriptional biomarkers, as well as clinical information, was independently validated. Results Twenty-six pairs of biomarkers with G×G interactions and two biomarkers with main effects were significantly associated with NSCLC survival. Compared with a model using clinical information only, the accuracy of the epigenetic and transcriptional biomarker-based prognostic model, measured by area under the receiver operating characteristic curve (AUC), increased by 35.38% (95% CI, 27.09%-42.17%; P = 5.10 × 10–17) and 34.85% (95% CI, 26.33%-41.87%; P = 2.52 × 10–18) for 3- and 5-year survival, respectively, which exhibited a superior predictive ability for NSCLC survival (AUC3 year, 0.88 [95% CI, 0.83-0.93]; and AUC5 year, 0.89 [95% CI, 0.83-0.93]) in an independent Cancer Genome Atlas population. G×G interactions contributed a 65.2% and 91.3% increase in prediction accuracy for 3- and 5-year survival, respectively. Interpretation The integration of epigenetic and transcriptional biomarkers with main effects and G×G interactions significantly improves the accuracy of prognostic prediction of early-stage NSCLC survival. |
| وصف الملف: | application/pdf |
| تدمد: | 0012-3692 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c117fff2ce0d616406ee5b2896746360Test http://hdl.handle.net/10852/81002Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c117fff2ce0d616406ee5b2896746360 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00123692 |
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