Expression And Significance Of MEKK3 And NF-κB P50,NF-κB P65 In Prostate Cancer

Background: Prostate cancer is one of the most commonly diagnosed malignancies in men.In the worldwide,the new cases of prostate cancer ranks the second among all tumors,while,the incidence of prostate cancer in American and European developed countries has exceeded lung cancer,ranking first in male malignant tumors.There is a significant regional and ethnic differences in prostate cancer,the incidence and mortality of prostate cancer is lower in China compared with western countries,while with the accelerating aging of the social population,the westernization of lifestyle,the transformation of dietary structure and the improvement of medical diagnostic technology,the incidence of prostate cancer in China increased year by year.Therefore,explicit the pathogenesis of prostate cancer,to early diagnosis,treatment and prognosis evaluation of the prostate cancer are paid more and more attention.In recent years,many tumor markers have been found to be associated with the occurrence and progression of prostate cancer,but the specific pathogenesis of prostate cancer is still unclear.Mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3(MEKK3)is widely expressed in various tissues of mammals.It participates in the occurrence and progression of multiple tumors through effective activation of mitogen-activated protein kinases(MAPKs)and nuclear factor kappa B(NF-κB)signaling pathway.But the expression of MEKK3 in prostate cancer has not been reported.Objective: By detecting the expression of MEKK3,NF-κB p50,NF-κB p65 in prostate cancer and benign prostatic hyperplasia(BPH),to analyze the relationships between the clinicopathologic features of prostate cancer and them.To investigate the relationships and role of MEKK3 and NF-κB signaling pathway in the occurrence and progression of prostate cancer,and toprovide a theoretical basis for further elucidation of the pathogenesis of prostate cancer.Methods: The immunohistochemical(IHC)method of S-P was used to detect the expression of protein MEKK3,NF-κB p50,NF-κB p65 in 40 prostate cancer tissues and 40 benign prostate hyperplasia tissues.All the data was analysed by statistical software SPSS21.0,the difference was considered statistically significant when the P-value was less than 0.05.Results:1 Expression of MEKK3: MEKK3 was expressed in both prostate cancer and benign prostatic hyperplasia tissues,the positive expression rate was80.0%(32/40)and 5.0%(2/40)respectively,and the difference was statistically significant(P < 0.05).The positive expression rate in the group of high-Moderate differentiation(Gleason score ≤7)and poor differentiation(Gleason score 8~10)was 61.1%(11/18)and 95.5%(21/22)respectively,the difference was statistically significant(P < 0.05).The positive expression rate in the clinical stage of Ⅰ+Ⅱ and Ⅲ+Ⅳ was 63.2%(12/19)and 95.2%(20/21)respectively,the difference was statistically significant(P < 0.05).2 Expression of NF-κB p50: NF-κB p50 was expressed in both prostate cancer and benign prostatic hyperplasia tissues,the positive expression rate was 75.0%(30/40)and 35.0%(14/40)respectively,and the difference was statistically significant(P < 0.05).The positive expression rate in the group of high-Moderate differentiation(Gleason score ≤7)and poor differentiation(Gleason score 8~10)was 50.0%(9/18)and 95.5%(21/22)respectively,the difference was statistically significant(P < 0.05).The positive expression rate in the clinical stage of Ⅰ+Ⅱ and Ⅲ+Ⅳ was 68.4%(13/19)and 81.0%(17/21)respectively,the difference has no statistically significant(P > 0.05).3 Expression of NF-κB p65: NF-κB p65 was expressed in both prostate cancer and benign prostatic hyperplasia tissues,the positive expression rate was 77.5%(31/40)and 2.5%(1/40)respectively,and the difference was statistically significant(P < 0.05).The positive expression rate in the group of high-Moderate differentiation(Gleason score ≤7)and poor differentiation(Gleason score 8~10)was 61.1%(11/18)and 90.9%(20/22)respectively,the difference has no statistically significant(P > 0.05).The positive expression rate in the clinical stage of Ⅰ+Ⅱ and Ⅲ+Ⅳ was 68.4%(13/19)and 85.7%(18/21)respectively,the difference has no statistically significant(P > 0.05).4 Correlations of MEKK3,NF-κB p50 and NF-κB p65 in prostate cancer:The Spearman rank correlation test showed that the expression of MEKK3,NF-κB p50 and NF-κB p65 were positively correlated with each other in prostate cancer(P < 0.05).5 Relationships of MEKK3,NF-κB p50 and NF-κB p65 with the clinicopathologic features in prostate cancer: The Spearman rank correlation test showed that the expression of MEKK3,NF-κB p50 and NF-κB p65 had no correlation with the prostate volume,prostate specific antigen(PSA)and age.Conclusions:1 The expression of MEKK3 and NF-κB p50,NF-κB p65 protein in prostate cancer tissues was significantly higher than that in benign prostatic hyperplasia tissues,this indicates that they might be involved in the molecular mechanism of the occurrence and progression of prostate cancer.It is suggested that MEKK3 may be a new tumor marker for the diagnosis of prostate cancer,and has potential clinical value.2 NF-κB p50 and NF-κB p65 are the main components of the NF-κB signaling pathway,and the high expression of them suggesting the NF-κB signaling pathway has been activated.The expression of MEKK3,NF-κB p50 and NF-κB p65 in prostate cancer were positively correlated with each other,this demonstrates that MEKK3 may initiate the occurrence and progression of prostate cancer through activation of the NF-κB signaling pathway.3 The expression of MEKK3 was closely associated with the histological differentiation and the clinical stage of prostate cancer,the higher of the expression,the worse of the tissue differentiation and the later of the clinical stage,which suggests that MEKK3 may be a new indicator to assess the prognosis of prostate cancer patients.