From:  Biomarkers in renal cell carcinoma and their targeted therapies: a review
 

DNA methylation biomarkers in RCC and their underlying mechanism

BiomarkerSampleMethod of diagnosisMechanismReference
VHLBloodRestriction endonuclease qPCRVHL promoter methylation inactivates the VHL tumor suppressor gene which in turn regulates HIF protein and hence contributes to RCC carcinogenesis[29, 38]
RASSF1ABloodRestriction endonuclease qPCR; MSPHypermethylation of the RASSF1A promoter inactivates the RASSF1A tumor suppressor gene involved in DNA repair, cell cycle, and cell death[39]
PCDH17Urine, serum, and tissue samplesQuantitative MSP

PCDH methylation was linked to the downregulation of the PCDH17 tumor suppressor gene that functions through the regulation of cell-to-cell adhesion, growth control, and signal transduction

PCDH17 hypermethylation was linked to progression and shorter disease-free survival in RCC patients

[39, 40]
NEFHTissueRNA expression microarrayDNA methylation of NEFH promoter and loss of expression has been linked to the AKT/β-catenin pathway leading to increased glycolysis rates and changes in the mitochondria[41]
APCUrine and bloodQuantitative MSPAPC promoter methylation and subsequent loss of expression of the APC gene have been associated with nuclear β-catenin accumulation and p53 deficiency[42]
CDKN2A (p16)Urine, blood, and tissue Quantitative MSPCDKN2A methylation plays an important role in RCC metastasis by affecting the p16/p14 expression[43]
MGMTBlood, urine, and tissueQuantitative MSPPromoter methylation of MGMT inhibits the MGMT DNA repair gene[44]
TIMP3Blood, urine, and tissueQuantitative MSP; restriction endonuclease qPCRMethylation-associated silencing of TIMP3 has been associated with the acquisition of tumorigenesis as TIMP3 contributes to VEGF-mediated angiogenesis regulation[45]
ZNF677Blood, urine, and tissueMethylated RNA immunoprecipitation-sequencing (MeRIP-seq) and MeRIP-qPCRPromoter methylation of ZNF677 leads to ZNF677 silencing which functions as a tumor suppressor[46]
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qPCR: quantitative PCR; MSP: methylation specific PCR; AKT: v-akt murine thymoma viral oncogene homolog