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Genomics Score Based on Genome-Wide Network Analysis for Prediction of Survival in Gastric Cancer: A Novel Prognostic Signature
41 Pages Posted: 3 Dec 2019
More...Abstract
Purpose: Gastric cancer is a product of multiple genes abnormal, including modification of genetic and epigenetic. This study aims to integrate various biomolecules (miRNAs, mRNA and DNA methylation) into a genome-wide network and develops a nomogram to predict overall survival of GC.
Materials and methods: 329 cases with GC are screened from TCGA as a training cohort and a random 150 examples is validation cohort. A genome-wide network is constructed based on batch Cox regression and LASSO. Nomogram is established to predict 1, 3 and 5-year OS in training cohort, which is then assessed with calibration, discrimination and clinical usefulness in the validation cohort using R program. GO and KEGG analysis are performed to explain the function.
Results: A genomics score with 7 miRNAs, 8 mRNA and 19 DNA methylation sites then divided into 9 models is a prognostic factor in multivariate analysis. Incorporating the genomics score into the genomics-based nomograms performs better in the estimation of OS than any single biomarker and the traditional TNM staging system, which could add prognostic value to the TMN staging. Multiple molecules and pathways are revealed to be related to the genome-wide network using DAVID 6.8.
Conclusions: A genome-wide network is confirmed as a novel prognostic signature for GC, which could potentially play an important role in future clinical practice. New targets for gastric cancer may be detected from this gene network.
Funding: This work was supported by grants from: National Natural Science Foundation of China 81872013, 81672446 and The Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (2018J007).
Declaration of Interest: The authors declare no conflict of interest.
Ethical Approval: Since TCGA was a public-use database, no additional permission was required from the Ethics Committee. In addition, this study was deemed exempt from institutional review board approval by Nanfang Hospital of Southern Medical University (Guangzhou, China).
Keywords: gastric cancer, genome-wide network, miRNA, mRNA, methylation, nomogram
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