The Correlation And Clinical Significance Of P504S And AR Expression In The Tumor Immune Microenvironment And Prognosis Of Prostate Cancer

BackgroundProstate cancer is one of the most common malignant tumors in men,and the incidence of prostate cancer ranks first in developed countries.With the development of economy and the change of people’s lifestyle in China,the incidence of prostate cancer has gradually increased.Prostate cancer is sensitive to androgen deprivation therapy at first,but it will eventually develop into castration resistant prostate cancer.The prognosis of mCRPC is poor and the treatment plan is limited.In recent years,immunotherapy represented by immunocheckpoint inhibitors(ICIs)has achieved lasting tumor suppression effect in some solid tumor patients.However,the clinical trials of several ICIs in prostate cancer have not achieved significant prognosis improvement.The mechanism of drug resistance and response of prostate cancer patients to ICIs has not been fully clarified,and markers that can predict the response of ICIs to prostate cancer are urgently needed in clinical practice.ObjectiveThis study intends to explore the role and potential mechanism of P63,P504S and AR in the microenvironment of prostate adenocarcinoma,and explore their predictive value for immunotherapy response and prognosis of prostate cancer,so as to provide a theoretical basis for screening patients with potential immunotherapy response.MethodGEPIA2 and TIMER 2.0 tools were used to analyze 499 prostate adenocarcinoma(PRAD)of TCGA,and getting the expression of P63 gene,P504S gene,and androgen receptor(AR)in prostate adenocarcinoma tissues.The immunohistochemical results of 94 patients with abnormally elevated PSA were retrospectively collected for verification.The results showed that P63 was negative in most prostate cancer tissues,and there was no significant difference.Therefore,we chose to explore the correlation between the expression of P504S,AR and the microenvironment of prostate cancer.The GEPIA 2 and HPA were used to analyze the correlation between the gene expression and the prognosis indicators of PRAD patients,such as overall survival,disease-free survival.TISIDB and TIMER 2.0 were used to analyze the correlation between gene expression and immune cell infiltration in PRAD microenvironment,and GEPIA 2 was used to analyze the correlation between gene expression and immunocheckpoint inhibitors.Through systematic review of relevant literature,potential molecular markers related to immune response to prostate cancer were predicted.Results1.GEPIA 2 and TIMER 2.0 showed that the expression of P504S in PRAD was significantly higher than that in normal tissues,and the expression of P63 was significantly lower than that in normal tissues;It was also verified by the immunohistochemical results of clinical patients,and the results were the same as those of biological information(P<0.05).2.GEPIA 2,TIMER 2.0 and immunohistochemical results of patients showed that the expression of AR in different prostate cancer was significantly different,and was related to the clinical stage of patients(P<0.05).Patients with higher clinical stage had stronger AR expression in the tumor.3.The expression of P63,P504S and AR in prostate tissue was correlated with patient’s age,prostate volume and PSA concentration(P<0.05).4.GEPIA 2 showed that the expression level of P504S was positively correlated with overall survival(OS),but not with disease free survival(DFS);The expression level of AR was negatively correlated with DFS,but not with OS.5.The expression of P504S and AR was correlated with the infiltration of immune cells in the tumor microenvironment.The expression of AR gene in PRAD was positively correlated with the infiltration of CD 8+T cells,Tregs and CAFs.It was negatively correlated with the infiltration of MDSCs(P<0.05);The expression of P504S gene in PRAD was negatively correlated with the infiltration of CD 8+T cells and CAFs(P<0.05),but not with Tregs and MDSCs(P>0.05).6.The expression of AR and P63 in PRAD was positively correlated with the expression of PD-L1.The expression of P504S was negatively correlated with the expression of PDL1(P<0.05).ConclusionThe expression of P504S and AR in prostate cancer is correlated with the degree of immune cell infiltration and the expression of PD-L1.P504S and AR may be the potential molecular markers for the response of immunotherapy and prognosis of prostate cancer.Patients with high AR expression and low P504S expression may be potential immunotherapy responders.