Exploring DNA Methylation in Tumour-adjacent Normal Prostate Tissue and Evaluating its Role as a Biomarker for PCa Detection

DNA methylation alterations as a result of field cancerization may be used as diagnostic biomarkers to improve Prostate Cancer (PCa) detection. To identify diagnostic biomarkers, we evaluated DNA methylation of KRTAP27-1, APC, HOXD3, CRIP3, KLK6 and RASSF1A in tumour, tumour-adjacent normal (TAN) and benign prostate tissue. DNA methylation of APC, RASSF1A and GSTP1 was detected in TAN tissue up to 8 mm from the tumour. KRTAP27-1 was discovered to be hypermethylated in TAN tissue using Global DNA methylation profiling. Overall methylation concordance of all genes between matched radical prostatectomy (RP) tumour and RP TAN or biopsy (Bx) TAN tissue was 81% and 66%, respectively. Hypermethylation of RASSF1A, KRTAP27-1 and HOXD3 in combination were most significantly associated with PCa (Benign vs. RP TAN: p = 5.87 x 10^-10, Benign vs. Bx TAN cases: p = 4.44 x 10^-8). My project demonstrates the benefit of using field cancerization biomarkers for PCa diagnosis.M.Sc