Machine learning-based integrative analysis of methylome and transcriptome identifies novel prognostic DNA methylation signature in uveal melanoma.

Journal: Briefings in bioinformatics
Published Date: Jul 20, 2021

Abstract

Uveal melanoma (UVM) is the most common primary intraocular human malignancy with a high mortality rate. Aberrant DNA methylation has rapidly emerged as a diagnostic and prognostic signature in many cancers. However, such DNA methylation signature available in UVM remains limited. In this study, we performed a genome-wide integrative analysis of methylome and transcriptome and identified 40 methylation-driven prognostic genes (MDPGs) associated with the tumorigenesis and progression of UVM. Then, we proposed a machine-learning-based discovery and validation strategy to identify a DNA methylation-driven signature (10MeSig) composing of 10 MDPGs (AZGP1, BAI1, CCDC74A, FUT3, PLCD1, S100A4, SCN8A, SEMA3B, SLC25A38 and SLC44A3), which stratified 80 patients of the discovery cohort into two risk subtypes with significantly different overall survival (HR = 29, 95% CI: 6.7-126, P < 0.001). The 10MeSig was validated subsequently in an independent cohort with 57 patients and yielded a similar prognostic value (HR = 2.1, 95% CI: 1.2-3.7, P = 0.006). Multivariable Cox regression analysis showed that the 10MeSig is an independent predictive factor for the survival of patients with UVM. With a prospective validation study, this 10MeSig will improve clinical decisions and provide new insights into the pathogenesis of UVM.

Authors

  • Ping Hou
    School for Environment and Sustainability, University of Michigan, Ann Arbor, MI, USA; Michigan Institute for Computational Discovery & Engineering, University of Michigan, Ann Arbor, MI, USA.
  • Siqi Bao
  • Dandan Fan
    Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China.
  • Congcong Yan
    School of Biomedical Engineering, Wenzhou Medical University.
  • Jianzhong Su
    Department of Mathematics, University of Texas at Arlington, Arlington, TX, 76019-0408, USA.
  • Jia Qu
    National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China. Electronic address: jia.qu@163.com.
  • Meng Zhou
    College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, People's Republic of China. biofomeng@hotmail.com.

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