Preliminary Study On LncRNA CYTOR Promotes The Resistance To Abirateronein CRPC

Objective: With the acceleration of the aging process of the population and the change of more westernized lifestyles,prostate cancer has shown a rising trend in China.Prostate cancer metastasis or castration resistance is currently the most difficult problem in clinical treatment.There were many clinical treatments for prostate cancer,Lncluding surgery,endocrine therapy,chemotherapy,radiation therapy,and immunotherapy.Abiraterone and prednisone combined with ADT can significantly improve the survival of patients with m HSPC compared with ADT alone.Abiraterone was also approved by the FDA as an effective drug for m CRPC before chemotherapy and m CRPC for chemotherapy failure.However,the occurrence of Abiraterone acquired resistance has severely affected the survival of these patients.The main purpose of this study is to explore important abnormal biological events that occur during the development of Abiraterone resistance in prostate cancer,and to clarify its possible the mechanism of Abiraterone resistance in prostate cancer.In order to find the sensitivity index to predict the treatment effect of abiraterone.Methods: In our previous research,we screened and confirmed LncRNAs through LNcap and LNcap-AI.After verification through systematic basic research,we screened and confirmed that CYTOR plays an important role in hormone resistance of prostate cancer.In this study,firstly,we subdivided into LNcap AD P40 from the LNcap and LNcap AI constructed by our laboratory.q RT-PCR was used to detect the levels of CYTOR and AR-V7,and Western blotting was used to detect the protein level of AR-V7.Then,we collected information and clinical samples from 90 patients who applied abiraterone clinically,Lncluding urine samples,blood samples,and tissues of clinical patients.According to the clinical characteristics of patients and the PSA-PFS after abiraterone treatment,the PSA response rate was an observation index.The 60 patients were divided into two groups: Abiraterone-S and Abiraterone-R.By extracting RNA from clinical urine samples and applying q RT-PCR to the level of CYTOR in the samples.Then the serum from clinical blood samples was extracted,RNA was extracted,and the level of CYTOR was detected by q RT-PCR after reverse transcription.Circulating Tumor Cell was extracted from the blood of clinical patients,and the circulating tumor cell probe was designed to detect the level of CYTOR in CTCS.Finally,the next-generation RNA in situ hybridization technology RNA-scope was used to detect the expression level of CYTOR in clinical tissue samples.Based on the clinical follow-up data of patients,the relationship between the transcription level of CYTOR and the effect of abiraterone was analyzed.Therefore,the feasibility of LncRNA CYTOR as a sensitive indicator of the efficacy of abiraterone in the treatment of prostate cancer was explored.Results:The level of CYTOR in LNcap,LNcap AD P40 and LNcap AI was positively correlated with the level of AR-V7,the level of CYTOR was highest in LNcap AI,and the level of CYTOR in LNcap was the lowest(P <0.01);The changes in protein expression levels were consistent with RNA levels,with the highest in LNcap AI and the lowest in LNcap(P <0.05).In 60 clinical urine samples of prostate cancer,the level of CYTOR was highest in Abiraterone-R.The levels of AR-V7 and CYTOR were consistent.CYTOR levels in clinical blood specimens were negative,and LncRNA CYTOR levels in the three groups of specimens were extremely low with no statistical difference.The change of CYTOR detection levels in 60 clinical blood CTC specimens was consistent with the urine test results.CYTOR was highest in the Abiraterone-R group(P <0.001).The results of RNAscope showed that the content of CYTOR in Abiraterone-R tissue was higher than that in Abiraterone-S group(P<0.01).Conclusion: The level of CYTOR is closely related to the abiraterone effect of prostate cancer.A high level of CYTOR indicated a poor treatment effect of abiraterone,while a low level of CYTOR indicated that the application of abiraterone will achieve good results.Detection of CYTOR levels in CTCs in urine and blood of clinical samples has strong clinical significance.Direct detection of serum CYTOR levels in serum cannot be an indicator of abiraterone efficacy.This study provided a clinically sensitive indicator of the therapeutic effect of abiraterone in prostate cancer,and the level of CYTOR had a strong guiding significance.