Association Between Serum Sex Hormones And Prostate Cancer Progression And Prognosis

Objectie: To investigate the association between serum sex hormones and prostate cancer progression and prognosis.Methods: A total of 167 PCa patients performed laparoscopic radical prostatectomy whose biopsy GS?6,clinical stage?T2c and prostate specific antigen(PSA)<10ng/ml were enrolled in this study.Data including age,preoperative PSA level,BMI,comorbidities,clinical presentation and preoperative serum total testosterone(TT)level were collected.Meanwhile,biopsy Gleason Score,clinical stage,radical Gleason Score and pathology stage were also collected.FSHR expression of BPH-1,LNCaP and PC3 cell lines was tested by Q-PCR and Western blot.We detected the proliferation and migration of LNCaP and PC3 cell lines which were treated with 1 ?g/ml FSH or 0?g/ml FSH by CCK-8 and Migration array as well as the expression of HIF-1? and VEGF in PC3.At last,we dectected the phosphorylation level of AKT and mTOR in PC3 cell line treated with 1?g/ml FSH or 0?g/ml FSH.Results: As both continuous and categorical variables,low serum testosterone was confirmed to be an independent predictor of pathological upgrading(P=0.01 and P=0.01)and upstaging(P=0.01 and P=0.02)after RP.PC3 expressed stronger FSHR mRNA compared with LNCaP,with no expression in BPH.When treated with 1?g/ml FSH,PC3 proliferation and migration were significantly promoted compared with treated with 0?g/ml FSH by CCK8 assay.The expression of HIF-1? and VEGF and the phosphorylation level of AKT and mTOR in PC3 were also improved.After treatment of mTOR inhibitor Rapamycin,proliferation of PC3 treated with FSH declined significantly,and HIF-1? and VEGF in PC3 declined greatly.Conclusion: Patients with low serum testosterone were more easily to have upgrading and upstaging.FSHR was mostly expressed in prostate cancer cell lines and FSH stimulated lethal PCa proliferation and migration via AKT/mTOR signaling by increased expression of HIF-1 and VEGF.Significance: This study associated serum testosterone and upgrading or upstaging,and enabled us to evaluate the real garade and stage.It is so important for us to acknowledge malignancy grade of prostate cancer to enable patients to get a better prognosis.Meanwhile,we firstly demonstrated that specific mechanism of role of FSH on proliferation and migration of prostate cacner.It may be a new therapeutic target of prostate cancer and be possible to reveal the association between serum sex hormones and prostate cancer progression and prognosis.