1. Marker Studya Method Specimen LoE
ADAMTS18
ARH1
Casp-8
CTNNB1
Dkk3
ESR1
ESR2
HOXA9
IGFBP3
ITGA9
LRRC3B
MDR1
MST1R
Xu, 2015
Costa, 2007
Christoph, 2008
Urakami, 2006b
Pires-Luís, 2017b
Christoph, 2008b
Skrypkina, 2016
Pires-Luís, 2015b
MSP, BGS
qMSP
MSP
Tissue
Blood IV
III
III/IV
Supplementary Figure 1. Forest plot of diagnostic RCC methylation markers and multi-marker panels that were investigated in a single study.
Forest plots of genomic location, sensitivity and specificity associated with RCC diagnosis for single markers (A) and multi-marker panels (B) and corresponding LoE.
a Sensitivities and specificities calculated from percentage of methylated samples. b Actual sensitivities and specificities.
Abbreviations: ccRCC, clear cell renal cell carcinoma; chRCC, chromophobe renal cell carcinoma; CI, confidence interval; LoE, Level of Evidence; MSP, methylation specific polymerase chain reaction; pRCC, papillary renal cell carcinoma; qMSP, quantitative methylation specific polymerase chain reaction; qPCR, quantitative polymerase chain reaction; RCC, renal cell carcinoma.

2.
Sensitivity (95% CI)
MTHFR
OXR1
PCDH17
RIZ1
SFN
sFRP1
sFRP2
sFRP4
sFPR5
SPARC
Wif1
Costa, 2007
Pires-Luís, 2017b
Costa, 2011
Ge, 2015
Urakami, 2006b
Ahmad, 2012
qMSP
MSP
Tissue
Blood
III
III/IV IV
Supplementary figure 1. Forest plot of diagnostic RCC methylation markers and multi-marker panels that were investigated in a single study.
Forest plots of genomic location, sensitivity and specificity associated with RCC diagnosis for single markers (A) and multi-marker panels (B) and corresponding LoE.
a Sensitivities and specificities calculated from percentage of methylated samples. b Actual sensitivities and specificities.
Abbreviations: ccRCC, clear cell renal cell carcinoma; chRCC, chromophobe renal cell carcinoma; CI, confidence interval; LoE, Level of Evidence; MSP, methylation specific polymerase chain reaction; pRCC, papillary renal cell carcinoma; qMSP, quantitative methylation specific polymerase chain reaction; qPCR, quantitative polymerase chain reaction; RCC, renal cell carcinoma.
Specificity (95% CI)

3. Marker Studya Method Specimen LoEB
Panel APC or GSTP1
Panel APC or PTGS2
Panel APC or RARb2
Panel OXR1 and MST1R
Panel sFRP1, sFRP2, sFRP4, sFRP5, Wif1, Dkk3
Panel VHL, CDKN2A (p16), CDKN2A (p14), APC, RASSF1A, TIMP3
Panel PDCH17 and TCF21
Panel PTSG2 or GSTP1
Panel RAFFF1A or FHIT
Hauser, 2013b
Pires-Luís, 2017b
Restriction endonuclease q-PCR
qMSP
Blood
Tissue
III
III/IV
Urakami, 2006b
Battagli, 2003
Costa, 2011
Hauser, 2013b
Skrypkina, 2016
MSP
qMSP
Restriction endonuclease q-PCR
Tissue
Urine
Blood IV
III
Supplementary figure 1. Forest plot of diagnostic RCC methylation markers and multi-marker panels that were investigated in a single study.
Forest plots of genomic location, sensitivity and specificity associated with RCC diagnosis for single markers (A) and multi-marker panels (B) and corresponding LoE.
a Sensitivities and specificities calculated from percentage of methylated samples. b Actual sensitivities and specificities.
Abbreviations: ccRCC, clear cell renal cell carcinoma; chRCC, chromophobe renal cell carcinoma; CI, confidence interval; LoE, Level of Evidence; MSP, methylation specific polymerase chain reaction; pRCC, papillary renal cell carcinoma; qMSP, quantitative methylation specific polymerase chain reaction; qPCR, quantitative polymerase chain reaction; RCC, renal cell carcinoma.
Panel RASSF1A or APC
Panel RASSF1A or FHIT or APC
Sensitivity (95% CI)
Specificity (95% CI)
General RCC
ccRCC
pRCC
chRCC Oncocytoma
n ≤ 50
n = 51-99
n ≥ 100
Compared to oncocytoma