An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese
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Yongqiang Wang1,2,*, Yuan Yu3,*, Rui Ye3,*, Duo Zhang3,*, Qiaoling Li3, Dan An3, Lu Fang4, Youcheng Lin5, Yong Hou3, Abai Xu5, Yu Fu6, Wei Lu4, Xin Chen1, Mingwei Chen4, Meng Zhang4, Huiling Jiang7, Chuanxia Zhang8, Pei Dong1, Chong Li9, Jun Chen10, Guosheng Yang6, Chunxiao Liu5, Zhiming Cai11, Fangjian Zhou1, Song Wu2,11
1Department 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
2The Affiliated Luohu Hospital of Shenzhen University, Shenzhen Luohu Hospital Group, Shenzhen 518000, China
3BGI-Shenzhen, Shenzhen 518083, China
4Anhui Medical University, Hefei 230032, China
5Department of Urology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China
6The Second People’s Hospital of Guangdong Province, Guangzhou 510310, China
7The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
8Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China
9CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
10The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China
11Department of Urological Surgery, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen 518000, China
*These authors contributed equally to this work
Song Wu, e-mail: firstname.lastname@example.org
Fangjian Zhou, e-mail: email@example.com
Keywords: bladder cancer, epigenetics, methylation, biomarkers, qMSP
Received: May 07, 2015 Accepted: November 20, 2015 Published: December 19, 2015
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.
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