Aberrant Expression Of Voltage-gated Chloride Ion Channel-2 Is Associated With Progression And Prognosis Of Prostate Cancer

Background and Objective:Prostate Cancer(PCa)is the common malignant tumor of the male genitourinary system.In recent years,the incidence rate of PCa has increased significantly in China.Traditional indicators such as PSA still cannot accurately judge and assess the progress and prognosis of patients with prostate cancer.It is important to find some effective markers for treatment of PCa,basing on levels of genes and proteins.A bioinformatics research predicts voltage-gated chloride ion channel-2(CLCN2)may be used as a potential marker to distinguish PCa from non-PCa,and to determine whether PCa is indolent or progressing.We found that CLCN2 is closely related to cellular process and metabolic process,basing on the Cancer Genome Atlas(TCGA)database.There are no reports about the prognosis and progression of PCa on CLCN2,Therefore,we intend to explore the expression level of CLCN2 in PCa,the relationship between CLCN2 and the clinicopathological characteristics and prognosis of PCa patients,and its mechanism of CLCN2 in cell proliferation,invasion and metabolism of PCa.Materials and Methods:Immunohistochemical staining of prostate tissue microarray was used to detect the difference of protein expression of CLCN2 between PCa and benign prostate tissues.The relationship between clinicopathological characteristics and prognosis of PCa patients and the expression of CLCN2 was analyzed by TCGA and Taylor databases.Cellular experiments were performed to examine the effect on the cellular and metabolic processes when the expression of CLCN2 was decreased in PCa.Results:1.The expression of CLCN2 was higher in PCa tissues(P= 0.035),and CLCN2 expression level in Gleason score(GS)> 7 was significantly higher than that in GS? 7(P=0.047).The high expression of CLCN2 in TCGA database was significantly related to serum PSA,GS,pathological grade,Tumor stage and metastasis(P= 0.024,P< 0.000,P= 0.002,P=0.035,P= 0.014).The high expression of CLCN2 in Taylor database was significantly related to metastasis(P= 0.008).2.Kaplan-Meier survival analysis based on TCGA and Taylor databases found that CLCN2 high expression and low expression have significant statistical differences in BCR free survival time and Overall survival time(P<0.000,P= 0.034,P= 0.021,P= 0.822).Multivariate COX proportional hazards models indentified CLCN2 gene expression level(P=0.046),PSA level(P<0.000)and pathological grade(P= 0.001)in TCGA database and CLCN2 gene expression level(P = 0.042),Gleason score(P= 0.011)and metastasis(P< 0.000)in Taylor database were independent predictors of biochemical recurrence risk after radical prostatectomy.3.The decreased expression of CLCN2 inhibits cell proliferation,migration and invasion,but prolongs cell cycle and promotes apoptosis in PCa.4.The decreased expression of CLCN2 inhibits glucolytic metabolism and mitochondrial metabolism in PCa.Conclusions:1.The high expression of CLCN2 promotes the occurrence and progression of PCa and is an independent predictor of the risk of biochemical recurrence and metastasis after radical prostatectomy.2.The analysis of the expression of CLCN2 in patients with PCa can predicts the probability of early biochemical recurrence.It may provide effective informations for the treatment and help to make a personalized treatment plan in PCa.