TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a simultaneous detection of urological cancers

• Published in: Epigenetics 2011-09, Vol.6 (9), p.1120-1130
• Main Authors: Costa, Vera L., Henrique, Rui, Danielsen, Stine Aske, Eknaes, Mette, Patrício, Patrícia, Morais, António, Oliveira, Jorge, Lothe, Ragnhild A., Teixeira, Manuel R., Lind, Guro E., Jerónimo, Carmen
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; Binding; Biology; Biomarkers - metabolism; Bioscience; Cadherins - genetics; Cadherins - metabolism; Calcium; Cancer; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - metabolism; Case-Control Studies; Cell; Cell Line, Tumor; Cycle; DNA Methylation - drug effects; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Hydroxamic Acids - pharmacology; Landes; Male; Middle Aged; Organogenesis; Promoter Regions, Genetic; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Proteins; ROC Curve; Sensitivity and Specificity; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism
• ISSN: 1559-2294; 1559-2308
• DOI: 10.4161/epi.6.9.16376

The three main types of urological cancers are mostly curable by surgical resection, if early detected. We aimed to identify novel DNA methylation biomarkers common to these three urological cancers, potentially suitable for non-invasive testing. From a candidate list of markers created after gene expression assessment of pharmacologically treated cell lines and tissue samples, two genes were selected for further validation. Methylation levels of these genes were quantified in a total of 12 cancer cell lines and 318 clinical samples. PCDH17 and TCF21 methylation levels provided a sensitivity rate of 92% for bladder cancer, 67% for renal cell tumors and 96% for prostate cancer. Methylation levels were significantly different from those of cancer free individuals (n = 37) for all tumor types (p < 0.001), providing 83% sensitivity and 100% specificity for cancer detection. Although in urine samples the sensitivity was 60%, 32% and 26% for bladder, renal, and prostate tumors, respectively (39% overall), absolute specificity was retained. We identified novel and highly specific methylation markers common to the three main urological cancers. However, additional efforts are required to increase the assay's sensitivity, enabling the simultaneous non-invasive screening of urological tumors in a single voided urine analysis.