WFRF:(You Dongfang)
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Trans-omics biomarker model improves prognostic prediction accuracy for early-stage lung adenocarcinoma
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- Dong, Xuesi (author)
- Nanjing Medical University,Southeast University
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- Zhang, Ruyang (author)
- Harvard University,Nanjing Medical University,Nanjing University
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- He, Jieyu (author)
- Nanjing Medical University
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- (creator_code:org_t)
- 2019-08-21
- 2019
- English 24 s.
- In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:16, s. 6312-6335
- Journal article (peer-reviewed)
Abstract
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- Limited studies have focused on developing prognostic models with trans-omics biomarkers for early-stage lung adenocarcinoma (LUAD). We performed integrative analysis of clinical information, DNA methylation, and gene expression data using 825 early-stage LUAD patients from 5 cohorts. Ranger algorithm was used to screen prognosis-associated biomarkers, which were confirmed with a validation phase. Clinical and biomarker information was fused using an iCluster plus algorithm, which significantly distinguished patients into high- and low-mortality risk groups (Pdiscovery = 0.01 and Pvalidation = 2.71×10-3). Further, potential functional DNA methylation-gene expression-overall survival pathways were evaluated by causal mediation analysis. The effect of DNA methylation level on LUAD survival was significantly mediated through gene expression level. By adding DNA methylation and gene expression biomarkers to a model of only clinical data, the AUCs of the trans-omics model improved by 18.3% (to 87.2%) and 16.4% (to 85.3%) in discovery and validation phases, respectively. Further, concordance index of the nomogram was 0.81 and 0.77 in discovery and validation phases, respectively. Based on systematic review of published literatures, our model was superior to all existing models for early-stage LUAD. In summary, our trans-omics model may help physicians accurately identify patients with high mortality risk.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- DNA methylation
- early-stage
- gene expression
- lung adenocarcinoma
- prognostic prediction
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- ref (subject category)
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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- Articles in the publication
- Aging
- By the university
- Lund University
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