Dataset Information

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

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.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4823069 | biostudies-other | 2016 Jan

REPOSITORIES: biostudies-other

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

Wang Yongqiang Y Yu Yuan Y Ye Rui R Zhang Duo D Li Qiaoling Q An Dan D Fang Lu L Lin Youcheng Y Hou Yong Y Xu Abai A Fu Yu Y Lu Wei W Chen Xin X Chen Mingwei M Zhang Meng M Jiang Huiling H Zhang Chuanxia C Dong Pei P Li Chong C Chen Jun J Yang Guosheng G Liu Chunxiao C Cai Zhiming Z Zhou Fangjian F Wu Song S

Oncotarget 20160101 3

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) pa ...[more]

PMID: 26700620

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Project description:Purpose: Determine if gene expression profiles in urine sediment could provide non-invasive candidate markers for painful bladder syndrome (PBS) with and/or without Hunner lesions. Materials and Methods: Fresh catheterized urine was collected and centrifuged from control (n = 5), lesion-free (n = 5), and Hunner lesion bearing (n = 3) patients. RNA was extracted from the pelleted material and quantified by gene expression microarray (Affymetrix Human Gene ST Array). Results: Three biologically likely hypotheses were tested: A) all three groups are distinct from one another; B) controls are distinct from both types of PBS patients combined, and C) Hunner lesion PBS patients are distinct from controls and non-Hunner-lesion PBS combined. For statistical parity an unlikely fourth hypothesis was included: non-Hunner-lesion PBS patients are distinct from controls and Hunner lesion PBS combined. Analyses supported selective upregulation of genes in the Hunner lesion PBS group (hypothesis C), and these were primarily associated with inflammatory function. This profile is similar to that reported in a prior microarray study of bladder biopsies in Hunner lesion PBS. Conclusions: Urine sediment gene expression from non-Hunner-lesion PBS patients lacked a clear difference from that of control subjects, while the array signatures from PBS patients with Hunner lesions showed a clear, primarily inflammatory, signature. This signature was highly similar to that seen in a prior microarray study of bladder biopsies. Thus, although sample sizes were small, this work suggests that gene expression in urine sediment may provide a non-invasive biomarker for Hunner lesion, but not non-Hunner lesion, PBS. Urine (40-100 ml) was immediately placed on ice, transported to the laboratory and centrifuged at -4C for 5 minutes. Pellets were washed twice with ice-cold phosphate-buffered saline, suspended in 0.8 ml TRIzol and RNA was extracted according to the manufacturer's instructions. RNA was stored at -80oC until all samples had been collected, then analyzed at our Microarray Core Facility using the Affymetrix GeneChip Whole Transcript (WT) Sense Target Labeling Assay protocol, added to Human Gene 1.0 ST array chips, and annotated with gene symbol and functional information (Affymetrix). Probe level data were produced by Partek GS (6.10) using the gcRMA output option. Probe set signal intensities < 4.2 were considered absent, and if > 10 chips rated a probe set absent, that probe set was not considered for further analysis. Additionally, probe sets that did not have a gene symbol-level annotation (e.g., were considered 'hypothetical', or 'expressed sequence tags') were not considered for further analysis.

Dataset Information

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

Publications

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

Similar Datasets

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