Clinicopathological Significance And Prognostic Value Of LDHA Expression In Prostate Cancer Patients

Background:Cancer cells exhibit an altered metabolism, which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. LDHA, the critical enzyme responsible for transforming pyruvate into lactate in glycolysis, has been demonstrated to be up-regulated in many types of cancer and to give rise to more aggressive behavior by regulating proliferation and antiapoptosis. However, its expression in prostate cancer(PC) has not been characterized thoroughly. The purpose of this study was to clarify the expression and potential impact of LDHA in PC. Methods:This study included 88 patients who underwent transurethral electrovaporization of prostate or radical prostatectomy at the First Affiliated Hospital of Zhengzhou University. All patients were followed up for at least 3 years. Patient-derived paraffin embedded PC specimens were collected for immunohistochemistry(IHC). Overall survival(OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by Chi-square tests. We transfected shRNA into Ln Cap cells against LDHA. LDHA was analyzed real-time RT-PCR. Cell growth, cell migration, cell cycle and cell apoptosis were evaluated in vitro. Results:IHC showed that the expresssion of LDHA in PC was up-regulated, 87.5% of total cancer tissue specimens had LDHA staining. There was a positive correlation of LDHA expression with Gleason score, lymph node metastasis, UICC stage and properative PSA. Survival analysis demonstrated that high expression of LDHA in PC was associated with lower overall survival(OS). However, there is no significant differences between LDHA positive expression and LDHA strong positive expression in prostate cancer patients. Specific shRNA against LDHA in Ln Cap cell line retarded cell growth and migration in vitro. Furthermore,LDHA knockdown also cycle arrest in S, induce cell apoptosis. Conclusions:Our study indicated that the expresssion of LDHA in PC was up-regulated, positive expression of LDHA in PC was associated with lower OS. This suggest that LDH-A expression could be an independent prognostic risk factor in PC patients and LDHA might be a potential therapeutic target in prostate cancer.