| ObjectivesFor the difficulty and bottleneck of predicting the sensitivity of abiraterone for CRPC patients without reliable indexes,the coexpression genes of AR-V7 were studied and verified by bioinformatics analysis based on the effect of AR-FL and AR-V7 on the sensitivity of abiraterone.Materials and MethodsMaterials and Methods In this study,peripheral blood samples were collected from 40 CRPC patients who collect blood samples before taking oral abiraterone.The transcriptional levels of AR-FL,AR-V7 and ARv567es in peripheral blood were detected by qRTPCR and DDPCR on PAXgene platform.The co-expression of AR-V7 was analyzed by bioinformatics to screen out the co-expression gene.At the same time,the transcriptional level of AR-V7 related genes in blood samples was detected,the clinical data of patients were followed up,and the response rates of PSA-PFS and PSA were observed as the indexes.Kaplan-Meier method,COX multivariate regression model and ROC curve were used to analyze the relationship between transcriptional levels of transcriptional transcripts and the efficacy of abiraterone in patients with CRPC.(P<0.05).ResultsThe expression of AR-FL in peripheral blood of CRPC patients and normal subjects;AR-V7 mRNA could be expressed in normal subjects.To remove the background value,we divided CRPC patients into high-expression group and low-expression group with the ratio of AR-V7 as 0.30.ARv56 es mRNA was detected in 10 patients with CRPC,and ARv567es mRNA was also detected in normal controls.The PSA response rate was significantly lower in patients with high expression of AR-V7 than that in patients with low expression of PSA-PFS.The relationship between PSA-PFS and AR-FL,AR-V7 and ARv567es was studied.The results showed that AR-FL and ARv567es were not significantly associated with PSA-PFS(P>0.05).COX multiparameter analysis showed that HR of AR-V7 was 4.81,95%confidence interval:1.30-17.81,P=0.019,which suggested that AR-V7 might be an independent risk factor for PSA progression in CRPC patients.There was no significant relationship between age,PSA level,oligo-metastasis and ADT time and positive expression of AR-FL,AR-V7 and ARv567es(P>0.05).The copies of FOXM1,PLK1 and UBE2C were positively correlated with ARV7 by bioinformatic analysis and DDPCR.The results of COX regression showed that PLK1 and UBE2C might be related to PSA progression in CRPC patients.AR-V7 state combined with PLK1 and UBE2C multivariate analysis to draw ROC curve,the results showed that the AUC value of AR-V7 coexpression gene PLK1 and UBE2C was significantly higher than that of AR-V7 alone(AUC value of AR-V7 was 0.733;The AUC value of the combined analysis was 0.802),suggesting that AR-V7 combined with gene testing was more predictive of PSA progression in patients with CRPC after abiraterone treatment.ConclusionsThe positive expression of AR-FL,AR-V7,PLK1 and UBE2C in the peripheral blood of patients with CRPC before treatment with abiraterone may be related to the initial resistance of abiraterone,but the reliability of the positive expression of high AR-V7 still needs to be confirmed by large-scale prospective study.Detection of AR-V7 and its associated coexpressed genes in peripheral blood may be a tool for predicting the efficacy of abiraterone,but large-sample studies are still needed to verify its feasibility. |
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