Assessment of FGFR۲ gene CpG island hypomethylationin prostate cancer and benign prostate hypeplasiausing white blood cells

Background: Prostate cancer (PCa) is ۲nd most common neoplasmin men and is highly heterogeneous, with slow progressionto an extremely aggressive and fatal disease. Epigeneticchanges associated with the initiation of malignancy and tumorprogression are hallmarks of prostate cancer. Fibroblast growthfactor receptor ۲ (FGFR۲), a member of the FGFRs family, is atumor suppressor gene that is implicated in PCa through aberrantDNA methylation. However, it is unclear whether DNAmethylation of FGFR۲ in white blood cells (WBCs) is associatedwith PCa occurrence and progression. This is the firstblood-based study to determine the efficacy of FGFR۲ CpG Island methylation epigenetics as a biomarker with prognosticsignificance in prostate cancer and to evaluate PSA levels forPCa diagnosis and progression.Materials and Methods: This is the first study to investigateFGFR۲ CpG hypomethylation in the blood leukocytes of ۱۰۰men with prostate cancer (PCa) in comparison with ۵۰ menwith Benign Prostate Hyperplasia (BPH) and ۵۰ healthy menas normal controls (NCs) to evaluate FGFR۲ as a potential PCadiagnostic biomarker. DNA was extracted from the blood samplesof all ۲۰۰ participants. Methylation-Sensitive RestrictionEnzymes (MSRE-PCR) and Real-time PCR (RT-PCR) wereused to quantify changes in CpG methylation. Statistical analyseswere performed using IBM SPSS (version ۲۶.۰; IBM Corp.,Armonk, NY, USA) and for all graphs creation, GraphPad Prism۷.۰۰ (GraphPad Software, La Jolla, CA, USA) were used.Results: The study results demonstrated that FGFR۲ CpGIsland was significantly hypomethylated in PCa samples(p<۰.۰۰۰۱) compared to BPH samples. The FGFR۲ hypomethylationvalue corresponded to a cutoff of ۱۸.۳۳% with ۹۰.۷۷%sensitivity and ۹۶.۵۲% specificities; In PCa samples, there wasa significant correlation between hypomethylation and clinicopathologicalfactors of Tumor Stage (TS) (r= ۰.۹۲,p<۰.۰۰۰۱)and Grade (r= ۰.۹۴,p<۰.۰۰۰۱) .Conclusion: There was a significant difference in the hypomethylationlevels of FGFR۲ among PCa specimens, BPH,and a significant positive correlation with clinicopathologicalparameters of tumor stage and grade, which may be helpfulwith high sensitivity and specificity in the early diagnosis andscreening of PCa.

کلیدواژه ها:

Prostate Cancer ، FGFR۲ Gene ، Epigenetics ، Hypomethylation ، White Blood Cells