To identify a panel of epigenetic biomarkers for accurate bladder cancer detection in urine sediments.
Gene expression microarray analysis of bladder cancer cell lines treated with 5-aza-2'deoxycytidine and Trichostatin A as well as 26 tissue samples was used to identify a list of novel methylation candidates for bladder cancer. Methylation levels of candidate genes were quantified in four bladder cancer cell lines, 50 bladder cancer tissues, 20 normal bladder mucosas, and urine sediments from 51 bladder cancer patients and 20 healthy donors, 19 renal cancer patients and 20 prostate cancer patients. ROC curve analysis was used to assess the diagnostic performance of the gene panel.
GDF15, HSPA2, TMEFF2, and VIM were identified as epigenetic biomarkers for bladder cancer. The methylation levels were significantly higher in bladder cancer tissues compared to normal bladder mucosa (P < 0.001) and the cancer-specificity was retained in urine sediments (P < 0.001). A methylation panel comprising GDF15, TMEFF2 and VIM correctly identified bladder cancer tissues with 100% sensitivity and specificity. In urine samples the panel achieved a sensitivity of 94% and specificity of 100% and an AUC of 0.975. The gene panel could discriminate bladder cancer from both healthy individuals and renal or prostate cancer patients (sensitivity: 94%, specificity: 90%).
By using a genome-wide approach, we have identified a biomarker panel that allows for early and accurate non-invasive detection of bladder cancer using urine samples.
PMID: 20975101 [PubMed - as supplied by publisher] Source: National Library of Medicine.