Differential expression and hypermethylation of apoptotic genes in circulating nucleic acids are associated with clinical phenotypes of prostate cancer and benign prostatic hyperplasia in Nigerians.

Abstract

Background: During carcinogenesis, cells have an increased ability to survive in the face of death-inducing mechanisms (apoptosis). Subversion of apoptosis is regarded as one of the primary factors helping the evolution of tumor cells. This study described the gene expression and DNA methylation of selected genes associated with apoptosis in prostate cancer (PCa) and benign prostatic hyperplasia (BPH).

Methods: The study involved a total of 195 participants: 65 with prostate cancer, 65 with BPH, and 65 apparently healthy controls. Circulating DNA/RNA was extracted using Qiagen kits. RNA was reverse transcribed to cDNA while the isolated DNA was treated with bisulfite. The expression of each gene was determined by a qPCR reaction and DNA methylation was quantified using methylation-specific quantitative PCR.

Results: We report differential expressions of BCL2, BOK, MCL1, and BAD genes in PCa group compared with controls(P < 0.05). The NOD1, CASP2, and CASP10 genes were differentially expressed(P < 0.05) in BPH and CASP7, CASP10, and MCL1 in PCa and BPH. A linear relationship exists between the expression of BCL2 and BOK and Gleason score in the PCa(P < 0.05). The expression of BOK gene shows a linear relationship with tumor burden(P < 0.05). There was an increase in methylation of BOK and ESR1 in PCa compared to BPH and controls(P < 0.05).

Conclusion: We describe a differential expression of BCL2, BOK, BAD, and MCL1 and methylation of BOK and ESR1 genes in PCa in this study population for the first time. These differentially expressed and methylated genes can be explored for differential diagnosis, monitoring of treatment and new therapeutic targets.