MPC1 and MPC2 expressions are associated with favorable clinical outcomes in prostate cancer

BMC Cancer

Research Article

Zhirui Fan¹  Mingzhi Zhang¹  Yasai Ji¹  Yali Zhong¹  Jing Zhao¹  Xiaoli Li²  Zhenhe Suo²  Yaqing Li²  Jing Cao³  Jahn M. Nesland⁴  Xiaoran Li⁴  Gaoyang Han⁵  Mariusz Adam Goscinski⁶  Jianguo Wen⁷ 

[1] Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Montebello, Oslo, Norway;Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;Department of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo, Montebello, Oslo, Norway;Department of Thoracic Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui City, Henan Province, China;Departments of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway;The Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China;

关键词: MPC1;    MPC2;    Mitochondrial;    Pyruvate;    Prostate cancer;   

DOI  :  10.1186/s12885-016-2941-6

 received in 2016-06-23, accepted in 2016-10-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCancer cells exhibit an altered metabolism, which is characterized by a preference for aerobic glycolysis more than mitochondrial oxidation of pyruvate. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) play a bottleneck role by transporting pyruvate into mitochondrial through the mitochondrial inner membrane. Therefore, their protein expression in cancers may be of clinical consequences. There are studies showing low levels of MPC1 expression in colon, kidney and lung cancers, and the expression of MPC1 correlates with poor prognosis. However, the expression status of MPC1 and MPC2 in prostate cancer (PCA) is unclear.MethodsIn this study, expression of MPC1 and MPC2 in LNCaP and DU145 prostate cancer cell lines was examined by immunocytochemistry (ICC) and Western blotting. Compared to the LNCaP cells, lower levels of MPC1 and MPC2 expression in the DU145 cell line was identified. We then extended our study to 88 patients with prostate cancer who underwent transurethral electro-vaporization of prostate or radical prostatectomy at the First Affiliated Hospital of Zhengzhou University, Henan, China. Patient-derived paraffin embedded PCA specimens were collected for immunohistochemistry (IHC). Correlations with clinicopathologic factors were evaluated by Chi-square or Fisher´s exact probability tests. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. The Cox proportional hazard regression model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis.ResultsLinear regression analysis revealed that MPC1 expression level was positively correlated with MPC2 expression (r = 0.375, P = 0.006) in the prostate cancers. MPC1 expression was negatively associated with UICC stage (P = 0.031). While UICC stage (P < 0.001) and lymph node metastasis (P = 0.002) were negatively associated with MPC2 expression. Positive MPC1 or MPC2 expression in cancer tissues was significantly associated with higher OS (P < 0.05). The multivariate analysis showed that both MPC1 and MPC2 expressions in PCA were independent prognostic factors for higher OS (For MPC1: RR = 0.654, 95% CI: 0.621-0690, P < 0.001; For MPC2: RR = 0.696, 95% CI: 0.660-0.734, P < 0.001).ConclusionsOur study indicates that MPC1 and MPC2 expressions are of prognostic values in PCAs and that positive expression of MPC1 or MPC2 is a predictor of favorable outcome.

【 授权许可】

CC BY   
© The Author(s). 2016