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

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

Author information

1
Department of Urology, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Guangzhou, 510060, China.
2
The Affiliated Luohu Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen 518000, China.
3
BGI-Shenzhen, Shenzhen 518083, China.
4
Anhui Medical University, Hefei 230032, China.
5
Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China.
6
The Second People's Hospital of Guangdong Province, Guangzhou 510310, China.
7
The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
8
Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China.
9
CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
10
The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.
11
Department of Urological Surgery, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China.

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

PMID:
26700620
PMCID:
PMC4823069
DOI:
10.18632/oncotarget.6666
[Indexed for MEDLINE]
Free PMC Article

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