Expression Of TRPM8,pSer9-GSK-3β,E-cadherin In Prostate Adenocarcinoma And Its Clinical Significance

Objectives: Prostate cancer is a common tumor in the male genitourinary system,and TRPM8 may regulate the epithelial-mesenchymal transition(EMT)process through the PI3K/Akt/GSK-3β pathway.In this study,we analyzed the expression of TRPM8,p Ser9-GSK-3β,EMT-related markers E-cadherin and Vimentin in prostate cancer and their clinicopathological significance,the possible role of EMT in the occurrence and development of prostate cancer was talked.METHODS:(1)The clinicopathological parameters of 166 cases of prostate acinar adenocarcinoma were collected,including age of onset,serum PSA level before radical operation,tumor volume ratio of radical resection specimens,Gleason score,ISUP grading group,TNM stage,positive margin and nerve invasion and vessel invasion;(2)Immunohistochemical technique was used to detect the expression levels of TRPM8,p Ser9-GSK-3β,E-cadherin,and Vimentin in 166 cases of prostate acinar adenocarcinoma;(3)The chi-square test and Fisher’s exact probability method were used to analyze the expression levels of TRPM8,p Ser9-GSK-3β,E-cadherin,Vimentin expression levels and their relationship with clinicopathological parameters;(4)Spearman correlation analysis was used to determine the correlation between TRPM8,p Ser9-GSK-3β,E-cadherin,Vimentin expression levels;(5)Using the kaplan-Meier method and the Cox proportional hazards regression model to analyze the factors affecting the biochemical recurrence-free survival of prostate cancer.RESULTS:(1)Clinicopathological data showed that the median age of onset of patients was 66 years old(IQR=62-72),the median serum PSA before radical operation was 14.96 ng/ml(IQR=8.03-30.00),and the tumor accounted for the percentage of prostate volume is19.2%(IQR=10.0-35.0).In addition,66.3% of patients had nerve invasion.According to the prognostic data,22.9% of the patients had biochemical recurrence after radical prostatectomy,and the median time of biochemical recurrence was 24 months(IQR=15.5-27.8).(2)The results of immunohistochemical staining showed that compared with normal prostate acinar epithelial cells,TRPM8 and p Ser9-GSK-3β were highly expressed in prostate acinar adenocarcinoma cells,and the high expression rates were79.52% and 74.10%,respectively.E-cadherin showed a low expression level,and the low expression rate was 66.87%.Vimentin was not expressed in normal prostate acinar epithelial cells and prostate cancer tumor cells;(3)The high expression of TRPM8 was more common in the group of patients with preoperative serum PSA level ≥25 ng/ml(P=0.035),and the group of patients with Gleason score ≥8 scores(P=0.011).The high expression of TRPM8 was more common in the group of patients with biochemical recurrence(P=0.038).High expression of p Ser9-GSK-3β was more common in patients with Gleason scores <8(P=0.033),tumor volume percentage <23%(P=0.002),no nerve invasion group(P=0.048),no vessel invasion group(P=0.009)and no biochemical recurrence group(P=0.030).Low expression of E-cadherin was more common in ISUP group 4～5(P=0.001),preoperative PSA ≥ 25ng/ml(P=0.020),Gleason scores ≥ 8(P<0.001),surgical margin positive patient group(P=0.008)and biochemical recurrence patient group(P=0.007);(4)There was a positive correlation between the expression of TRPM8 and p Ser9-GSK-3β(r=0.620,P<0.001);There was a negative correlation between TRPM8 and E-cadherin(r=-0.626,P<0.001);there is a negative correlation between the expression of p Ser9-GSK-3β and E-cadherin(r=-0.314,P<0.001);(5)The biochemical recurrance-free survival was significantly reduced in the group of patients <60 years old(P=0.001),the group of patients with Gleason score ≥8 points(P<0.001),the group of patients with tumor volume percentage ≥23%(P=0.015)and the group of patients with nerve invasion(P=0.004).Gleason scores ≥8 is an independent risk factor for decreased biochemical recurrence-free survival in prostate cancer patients(HR: 0.025;95%CI:0.003-0.188;P<0.001).Conclusion: High expression of TRPM8 and low expression of E-cadherin in prostate cancer indicated poor prognosis of prostate cancer.p Ser9-GSK-3β,as an inhibitory phosphorylation state of GSK-3β,is a protective factor for prognosis of prostate cancer.In this study,the low expression of E-cadherin in prostate cancer cells confirmed that prostate cancer has EMT,and the EMT process is involved in the invasion and disease progression of prostate cancer.There is a correlation between TRPM8,p Ser9-GSK-3β,and E-cadherin.