An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese

Oncotarget. 2016 Jan 19;7(3):2754-64. doi: 10.18632/oncotarget.6666.

Abstract

To develop a routine and effectual procedure of detecting bladder cancer (BlCa), an optimized combination of epigenetic biomarkers that work synergistically with high sensitivity and specificity is necessary. In this study, methylation levels of seven biomarkers (EOMES, GDF15, NID2, PCDH17, POU4F2, TCF21, and ZNF154) in 148 individuals-which including 58 urothelial cell carcinoma (UCC) patients, 20 infected urinary calculi (IUC) patients, 20 kidney cancer (KC) patients,20 prostate cancer (PC) patients, and 30 healthy volunteers (HV)-were quantified by qMSP using the urine sediment DNA. Receiver operating characteristic (ROC) curves were generated for each biomarker. The combining predictors of possible combinations were calculated through logistic regression model. Subsequently, ROC curves of the three best performing combinations were constructed. Then, we validated the three best performing combinations and POU4F2 in another 72 UCC, 21 IUC, 26 KC and 22 PC, and 23 HV urine samples. The combination of POU4F2/PCDH17 has yielded the highest sensitivity and specificity of 90.00% and 93.96% in all the 312 individuals, showing the capability of detecting BlCa effectively among pathologically varied sample groups.

Keywords: biomarkers; bladder cancer; epigenetics; methylation; qMSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / urine*
  • Cadherins / genetics*
  • China
  • DNA / genetics
  • DNA / urine
  • DNA Methylation / genetics*
  • Humans
  • Kidney Neoplasms / urine
  • Male
  • Prostatic Neoplasms / urine
  • Sensitivity and Specificity
  • Transcription Factor Brn-3B / genetics*
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / urine*
  • Urinary Calculi / urine
  • Urothelium / pathology

Substances

  • Biomarkers, Tumor
  • Cadherins
  • POU4F2 protein, human
  • Transcription Factor Brn-3B
  • protocadherin 17, human
  • DNA