CombinedRASSF1AandRASSF2APromoter Methylation Analysis as Diagnostic Biomarker for Bladder Cancer

摘要

Promoter hypermethylation, a widely studied epigenetic event known to influence gene expression levels, has been proposed as a potential biomarker in multiple types of cancer. Clinical diagnostic biomarkers are needed for reliable prediction of bladder cancer recurrence. In this paper, DNA promoter methylation of five C-terminal Ras-association family members (RASSF1A, RASSF2A, RASSF4, RASSF5, andRASSF6) was studied in 64 formalin-fixed paraffin-embedded (FFPE) bladder cancer and normal adjacent tissues using methylation-specific high-resolution melting (MS-HRM) analysis. Results showed that 73% (30/41) of transitional cell carcinoma, 100% (3/3) of squamous cell carcinoma, and 100% (4/4) of small cell carcinoma demonstrated promoter methylation of theRASSF1AorRASSF2Agene, but only 6% (1/16) of normal tissues had promoter methylation ofRASSFgenes. Testing positive for hypermethylation ofRASSF1AorRASSF2Apromoter provided 77% sensitivity and 94% specificity for identification of cancer tissues with an area under the curve of 0.854, suggesting that promoter methylation analysis ofRASSF1AandRASSF2Agenes has potential for use as a recurrence biomarker for bladder cancer patients.