engleski

RASSF1 gene methylation in prostate cancer patients

Prostate cancer (PC) is the most commonly diagnosed cancer in men and the 3rd leading cause of death in Europe. Serum prostate specific antigen (PSA) level is used as a PC biomarker in routine work but PSA is not a tumorspecific marker, it is tissue specific and blood levels are increased in non-malignant diseases such as benign prostatic hyperplasia (BPH) and prostatitis. In order to make a definitive diagnosis, patients with suspected prostate cancer undergo a prostate needle biopsy with only one third of patients having PC confirmed. This low PSA specificity leads to a large number of unnecessary biopsies, PC overdiagnosis, and a detection of indolent tumors and biopsyrelated side effects. To enhance PC detection, we have explored methylation patterns of cell free DNA (cfDNA) of RASSF1 gene in blood samples since its methylation is already included in a multiplex epigenetic assay performed on prostate biopsies. For this study paraffin embedded prostate tissue and blood of 50 patients with PC and 50 patients with BPH was utilized for extraction of genomic and cellfree DNA. Following bisulfite conversion, the region of RASSF1 is amplified via PCR and quantitatively degrees of methylation at nine CpG positions were analyzed by pyrosequencing. Methylation of RASSF1 gene in PC tissue was statistically significantly higher than in BPH tissue in all CpG positions. cfDNA methylation exhibited a similar DNA methylation pattern. Although cfDNA methylation as a biomarker in samples of liquid biopsies seems appealing, our results make us to rethink how to segregate and analyze just cfDNA originating from prostate since methylation of RASSF1 well distinguishes PC from BPH tissue. Additional work should be performed on other types of liquid biopsy; blood, serum or urine while it may be more prosperous.

RASSF1 methylation ; prostate cancer

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