Prognostic DNA methylation markers for renal cell carcinoma: a systematic review

• Published in: Epigenomics Vol. 9; no. 9; pp. 1243 - 1257
• Main Authors: Joosten, Sophie C, Deckers, Ivette AG, Aarts, Maureen J, Hoeben, Ann, van Roermund, Joep G, Smits, Kim M, Melotte, Veerle, van Engeland, Manon, Tjan-Heijnen, Vivianne C
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.09.2017
• Subjects: Biomarkers; Biomarkers, Tumor - genetics; Cadherins - genetics; Calcium-Binding Proteins - genetics; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; Data collection; Deoxyribonucleic acid; DNA; DNA Methylation; DNA-Binding Proteins - genetics; Epigenetics; Frizzled-related protein 1; GATA5 Transcription Factor - genetics; Gene expression; Genomes; Humans; Intercellular Signaling Peptides and Proteins - genetics; Kidney cancer; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Literature reviews; Medical prognosis; Membrane Proteins - genetics; Neurofilament Proteins - genetics; Patients; prognosis; promoter CpG island methylation; Promoter Regions, Genetic; Quality; Renal cell carcinoma; Studies; survival; Systematic review; Transcription Factors - genetics; Tumor markers; Tumor Suppressor Proteins - genetics; Tumorigenesis; Tumors; kidney cancer; promoter CpG island methylation; renal cell carcinoma; biomarkers; survival; DNA methylation; prognosis
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2017-0040

Despite numerous published prognostic methylation markers for renal cell carcinoma (RCC), none of these have yet changed patient management. Our aim is to systematically review and evaluate the literature on prognostic DNA methylation markers for RCC. We conducted an exhaustive search of PubMed, EMBASE and MEDLINE up to April 2017 and identified 49 publications. Studies were reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, assessed for their reporting quality using the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) criteria, and were graded to determine the level of evidence (LOE) for each biomarker. We identified promoter methylation of , , , , , , , and as promising prognostic markers. Extensive methodological heterogeneity across the included studies was observed, which hampers comparability and reproducibility of results, providing a possible explanation why these biomarkers do not reach the clinic. Potential prognostic methylation markers for RCC have been identified, but they require further validation in prospective studies to determine their true clinical value.