European Urology Oncology

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European Urology Oncology Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review  Kim Lommen, Nathalie Vaes, Maureen J. Aarts, Joep G. van Roermund, Leo J. Schouten, Egbert Oosterwijk, Veerle Melotte, Vivianne C. Tjan-Heijnen, Manon van Engeland, Kim M. Smits  European Urology Oncology  DOI: 10.1016/j.euo.2019.07.011 Copyright © 2019 The Authors Terms and Conditions

Fig. 1 PRISMA flow diagram visualising the study selection process. PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses. European Urology Oncology DOI: (10.1016/j.euo.2019.07.011) Copyright © 2019 The Authors Terms and Conditions

Fig. 2 Sum score of all articles per STARD item. STARD = Standards for Reporting of Diagnostic Accuracy Studies. European Urology Oncology DOI: (10.1016/j.euo.2019.07.011) Copyright © 2019 The Authors Terms and Conditions

Fig. 3 Forest plots of diagnostic RCC methylation markers that are independently validated in at least two studies. Forest plots of genomic location, sensitivity, and specificity associated with RCC diagnosis for (A) APAF1, (B) APC, (C) CDH1, (D) CDKN2A (p14), (E) CDKN2A (p16), (F) DAPK1, (G) FHIT, (H) GSTP1, (I) MGMT, (J) PTGS2, (K) RARb2, (L) RASSF1A, (M) TCF21, (N) TIMP3, and (O) VHL and corresponding LoE. ccRCC = clear cell renal cell carcinoma; chRCC = chromophobe renal cell carcinoma; CI = confidence interval; LoE = level of evidence; MSP = methylation specific polymerase chain reaction; n/a = not available; pRCC = papillary renal cell carcinoma; qMSP = quantitative methylation specific polymerase chain reaction; qPCR = quantitative polymerase chain reaction; RCC = renal cell carcinoma. a Sensitivities and specificities calculated from percentage of methylated samples. b Actual sensitivities and specificities. European Urology Oncology DOI: (10.1016/j.euo.2019.07.011) Copyright © 2019 The Authors Terms and Conditions

Fig. 4 Independently validated markers known to be involved or methylated in several human cancers. European Urology Oncology DOI: (10.1016/j.euo.2019.07.011) Copyright © 2019 The Authors Terms and Conditions

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