Expression And Significance Of GPER In Prostate Cancer

Objective To explore and analyze the expression and significance of G protein-coupled estrogen receptor(GPER)in prostate cancer.Methods From September 2020 to September 2022,40 tissue samples were collected from Ningxia Medical University’s patients with prostate cancer(PCa)who underwent radical prostatectomy and patients with benign prostatic hyperplasia(BPH)who underwent transurethral resection of the prostate.Collected clinical indicators of patients,compare the differences between the clinical indicators of BPH and PCa patients;Using immunohistochemical method to compare the localization and expression of GPER,ERK,NF-κB in tissue samples of BPH and PCa patients;Western-Blot detection The expression of GPER,ERK,and NF-κB proteins in BPH,PCa tissues and prostate-related cells(RWPE,BPH-1,C4-2B,DU145,TAXR,MDVR,DU145 R,LNCa P);correlation analysis clarified the relationship between GPER and BPH,Correlation of clinical indicators in PCa patients;bioinformatics analysis of correlations among GPER,ERK,and NF-κB in PCa.Results 1.Compared with BPH patients,PCa patients had lower BMI,prostate volume,total protein,albumin levels,IPSS score,and residual urine volume,and higher plasma T-PSA values(P<0.05),but age,fasting blood glucose,and PSA ratio were no significant difference(P>0.05);compared with Gleason 5-7 PCa patients,Gleason 8-10 group patients had lower residual urine volume and prostate volume(P<0.05),and there were no significant differences in other indicators(P<0.05).2.In the tissue samples of patients with BPH and PCa,GPER was expressed in epithelial and mesenchymal cells,and both cytoplasm and nucleus were positive,and the expression level of GPER was mainly in the nucleus;the expression level of GPER in BPH tissue was lower than that in PCa tissue(P<0.05);ERK and NF-κB were expressed in epithelial and mesenchymal cells of patients with BPH and PCa,and were positive in cytoplasm and nucleus,but there was no significant difference in the expression levels between BPH and PCa tissue samples(P>0.05).3.The protein expression level of GPER in BPH tissue was lower than that in PCa tissue(P<0.05),but there was no significant difference between Gleason5-7group and Gleason8-10 group in PCa patients(P>0.05).The protein expression levels of ERK and NF-κB did not show any significant difference between BPH and PCa patients(P<0.05).In PCa tissue,GPER expression level was positively correlated with prostate volume and T-PSA,negatively correlated with albumin level(P<0.05),and had no correlation with total protein level,residual urine volume,BMI,etc.(P>0.05).The expression level of NF-κB was only positively correlated with residual urine volume(P<0.05).There was no correlation between GPER expression level and clinical indicators of PCa patients in Gleason5-7 group(P>0.05);but in Gleason score 8-10 group of PCa patients,GPER expression level was correlated with prostate volume,T-PSA and residual urine volume(P<0.05).4.Bioinformatics suggested that in PCa,GPER was correlated with ERK,and ERK was correlated with NF-κB(RELA)(P<0.05).5.The results of Western-Blot experiments suggested that the expression level of GPER in hormoneinsensitive PCa cells C4-2B was significantly higher than that of prostate epithelial cells RWPE-1,prostatic hyperplasia cells BPH-1 and hormone-sensitive PCa cells LNCa P(P<0.05);The expression levels of ERK and NF-κB in C4-2B cells were significantly higher than those in RWPE and BPH-1 cells(P<0.05).The expression level of GPER in C4-2B cells was higher than that of docetaxel-resistant cell line TAXR and enzalutamide-resistant cell line MDVR(P<0.05).The expression level of GPER in prostate cancer cell line DU145 was higher than that in DU145docetaxel-resistant cell line DU145R(P<0.05).Conclusion GPER is involved in the occurrence and development of PCa,and it may play an important role in the process of resistance to docetaxel and enzalutamide in PCa;GPER may exert biological functions through ERK and NF-κB signaling pathways.