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 BNC1, SCUBE3, GATA5, SFRP1, GREM1, RASSF1A, PCDH8, LAD1 and NEFH 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.
Epigenomics. 2017 Aug 14 [Epub ahead of print]
Sophie C Joosten, Ivette Ag Deckers, Maureen J Aarts, Ann Hoeben, Joep G van Roermund, Kim M Smits, Veerle Melotte, Manon van Engeland, Vivianne C Tjan-Heijnen
Division of Medical Oncology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands., Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands., Department of Urology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.