title: TCF21 and PCDH17 methylation: An innovative panel of biomarkers for a simultaneous detection of urological cancers.
abstract: 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.
authors.affiliation: Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Porto, Portugal.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Costa
authors.forename: Rui
authors.initials: R
authors.lastname: Henrique
authors.forename: Stine Aske
authors.initials: SA
authors.lastname: Danielsen
authors.forename: Mette
authors.initials: M
authors.lastname: Eknaes
authors.forename: Patrícia
authors.initials: P
authors.lastname: Patrício
authors.forename: António
authors.initials: A
authors.lastname: Morais
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliveira
authors.forename: Ragnhild A
authors.initials: RA
authors.lastname: Lothe
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Guro E
authors.initials: GE
authors.lastname: Lind
authors.forename: Carmen
authors.initials: C
authors.lastname: Jerónimo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism
chemical_list: D001374:Azacitidine; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D015820:Cadherins; D000077209:Decitabine; D006877:Hydroxamic Acids; C529349:PCDH17 protein, human; C491825:TCF21 protein, human; C012589:trichostatin A