Meta-analysis Of The Association Between RASSF1A Promoter Methylation And Prostate Cancer

Purpose: The promoter methylation status of Ras-associated domain family 1A(RASSF1A)is closely related to the occurrence and development of prostate cancer.But due to the small sample size of individual studies,the diversity of sample sources and methylation detection methods,a clear and unified conclusion is still lacking.This study systematically explored the potential association of RASSF1 A gene promoter methylation status with PCa risk and its clinicopathological features such as Gleason Score,the preoperative PSA levels,and tumor stage in order to give inspirations for the early detection of prostate cancer and monitoring the progress of the disease.Methods: The computer comprehensively searched databases of CNKI,Wanfang,VIP,PubMed,EMBASE,CBM,Cochrane Library,and ISI Web of Science,to collect eligible case-control literature studies about the association of the incidence of RASSF1 A gene promoter methylation with PCa risk and its clinico pathological features in strict accordance with the literature inclusion and exclusion criteria.Compare the difference in the methylation status of the RASSF1 A gene promoter in tissues,blood,or urine of prostate cancer patients and non prostate cancer patients,and the difference of the incidence of RASSF1 A promoter methylation in prostate patients with different levels of Gleason Score,preoperative PSA and tumor grading.The ratio ratio is used as the effect quantity,and the effect quantity is expressed in 95% confidence interval.Revman5.3 software is used for data processing and analysis.Results : Finally,25 studies that met the current Meta analysis requirements were detected from 181 related studies.A total of 1,506 Pca patients and 946 benign prostatic hyperplasia(BPH)patients or healthy men were screened out.The literature was published from2002 to 2017.Of these,23 studies were included to assess the association between the frequency of RASSF1 A gene promoter methylation and PCa risk,Of which 14,nine and 12 studies gathered to assess the relationship between the frequency of RASSF1 A promoter methylation and Gleason Score,PSA levels,and tumor stage,respectively.The heterogeneity test results reveal that the studies are non-homogeneous,that is,there are differences.Therefore,the random effect model isused to combine the collected data and subgroup analysis was conducted based on sample sources,methylation detection methods and control group sources.Meta analysis statistics show that,in general,the frequency of RASSF1 A gene promoter methylation was significantly associated with PCa risk(OR = 12.08,95% CI 7.19�20.30,P<0.001)and Gleason score(OR=2.34,95% CI:1.49-3.66,P=0.005).Inaddition,subgroup stratification analysis based on different specimen sources showed that the significant association between the frequency of methylation of RASSF1 A gene and Gleason score(OR =2.69,95% CI:1.65�4.37,P= 0.007),PSA level(OR=3.12,95% CI:1.78�5.45,P= 0.17),and tumor stage(OR=1.87,95% CI:1.14�3.05,P= 0.02)in prostate tissue instead of urine in prostate cancer patients.Conclusions: The results of this meta analysis showed that the RASSF1 A promoter methylation rate was significantly associated with an increased risk for PCa.Furthermore,the methylation rate of the RASSF1 A gene was positively correlated with Gleason score,serum PSA level,and tumor stage in prostate tissue of prostate cancer.This indicates that the methylation rate of the RASSF1 A promoter can be used for the early diagnosis of prostate cancer and prognosis prediction of the disease.