Association of Tissue Promoter Methylation Levels of APC, RASSF1A, CYP26A1, and TBX15 with Prostate Cancer Progression

• Main Author: Liu, Li Yang
• Other Authors: Bapat, Bharati
• Language: en_ca
• Published: 2012
• Subjects: DNA Methylation; Prostate Cancer; Epigenetic Mechanism; Progression; Biochemical Recurrence; 0369; 0307
• Online Access: http://hdl.handle.net/1807/33724

Aberrant promoter methylation is known to silence tumor-suppressor genes in prostate cancer. Using a quantitative real-time PCR assay(MethyLight), I determined promoter methylation levels of APC, RASSF1A, CYP26A1 and TBX15 in 219 radical prostatectomies diagnosed between 1998-2001, examined their correlation with clinicopathological follow-up data including Gleason Pattern(GP), Gleason Score(GS) and pathological stage, and explored their potential in predicting biochemical recurrence(BR) using univariate and multivariate analyses. I demonstrated that methylation status of all four genes could accurately differentiate normal from cancerous tissues. Quantitative methylation levels of APC and TBX15 correlated strongly with GP, GS, and pathological stage. Both APC and TBX15 methylation levels could significantly predict BR in univariate analysis(p-value=0.028 and 0.003, respectively). The methylation profiles of APC and TBX15 combined could discriminate patients into high, intermediate, and low risk groups of BR(p-value=0.005). My project demonstrated that quantitative increase in promoter methylation levels of APC and TBX15 were associated with PCa progression.