Meta-Analysis And Preliminary Clinical Research On The Application Of CfDNA Concentration In Prostate Cancer

The first part:Meta-analysis of cfDNA concentration in the diagnosis and prognosis of prostate cancerObjective:The clinical outcomes of patients with different stages of prostate cancer(PCA)are different,and early diagnosis can effectively improve the prognosis of patients.The prostate specific antigen(PSA),which is a specific tumor marker for prostate,may be elevated in prostate hyperplasia,prostate inflammation,infection,etc,andoften leads to excessive diagnosis and treatment.Therefore,there is a pressing need to search for useful biomarkers for PCA diagnosis and prognosis.Cell free DNA(cfDNA)in the blood of prostate cancer patients is relatively high,which is a biomarker with potential application in the diagnosis and treatment of prostate cancer.However,due to various reasons,the utility of total cfDNA quantitation in PCA in clinical setting remains elusive.Here,we performed a thorough meta-analysis to assess the diagnostic and prognostic value of cfDNA concentration for patients with PCA.Method and materials:More than six databases,including Pub Med,Web of Science,Medline,PMC,EMBASE and the Cochrane Library,were searched.Results yielded all eligible articles from the date of inception to June 30,2020.The difference between PCA and control groups(benign prostatic hyperplasia group and healthy individuals),diagnostic and prognostic variables of cfDNA in PCA,especiallyin castration-resistant prostate cancer(CRPC)were included in the meta analyzed by STATA(version 15)and R(version 3.4.6).Then we explored the possibility of combined application of PSA and cfDNA to improve thediagnostic andprognostic efficacy of eachof them in PCA.Results:A total of 23 articles were enrolled in our meta-analysis: 69.6%(16/23)were related to diagnosis,and 56.5%(13/23)were related to prognosis.The earliest literature was published in 2004.The pooled concentration of cfDNA in PCA was significantly higher than that in the control group(SMD0.89,95%CI0.53,1.26),mirroring results for the prostatespecific antigen(PSA).For the detection test variables,the SROC with95%CI was 0.87(0.84,0.90)for cfDNA concentration.In terms of prognostic variables,the concentration of cfDNA were significantly related with progressionfree survival(PFS,log HR=0.84,95%CI0.39,1.28)and overall survival(OS,log HR=0.60,95%CI0.29,0.90),respectively.For CRPC,this correlation is even more obvious with PFS(log HR=0.65,95%CI0.33,0.98)and OS(log HR=0.59,95%CI0.34,0.83).Lastly,the test showed no significant publication bias in the present meta-analysis,excluding the diagnostic meta-analysis.The second part:The preliminary clinical study of plasma cfDNA concentration in the diagnosis of PCA.Objective: The meta-analysis shows the potential value of cfDNA concentration in the diagnosis of PCA.This study detects the plasma cfDNA concentration of PCA and its combination with PSA,then explores its significance in the clinical diagnosis.Methods: Peripheral blood samples of 18 healthy individuals(healthy individual group),28 patients with benign prostatic hyperplasia(BPH group),and 24 patients with prostate cancer(PCA group)were collected.The cfDNA was extracted by magnetic bead method,and quantified by fluorescence quantitative PCR method.The difference of cfDNA concentration in plasma between BPH,healthy individuals and PCA was analyzed by SPSS(version 25.0).The ROC curve was used to assess the diagnostic value of cfDNA and its combination with PSA for PCA.Then we explored the correlation between cfDNA concentration and the Gleason score.Results: The plasma cfDNA concentration of PCA group is significantly higher than that of BPH group and healthy individual group(P<0.05).The combination of cfDNA concentration and PSA was superior with the area under the ROC curve(AUC)0.792,95% CI0.678,0.905 compared with cfDNA or PSA alone0.790(0.677,0.903),0.650(0.514,0.787),respectively.When the combined predictor cut-off value of 199.50ng/ml was used to diagnose prostate cancer,the sensitivity was 83.3% and the specificity was 69.6%.There was no significant correlation between plasma cfDNA concentration and Gleason score.Conclusion: Plasma cfDNA can be used as a biomarker for PCA diagnosis and prognosis.The cfDNA concentration,especiallycombined with PSA,has a higher sensitivity and specificity than PSA alone.High concentration cfDNA werecorrelated with poor prognosis in PCA,especially in CRPC.The combined predictor of them is more valuable in the prognosisassessment of PCA.