Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients

Gaojie Liu, Jie Zhu, Menglei Yu, Canfeng Cai, Yu Zhou, Min Yu, Zhiqiang Fu, Yuanfeng Gong, Bin Yang, Yingru Li, Quanbo Zhou, Qin Lin, Huilin Ye, Liangtao Ye, Xiaohui Zhao, Zhihua Li, Rufu Chen, Fanghai Han, Chaoming Tang, Bing Zeng

Glutamate dehydrogenase (GDH) is a key enzyme that catalyzes the final reaction of the glutamine metabolic pathway, and has been reported implicated in tumor growth and metastasis. However, it's clinical significance and role in colorectal cancer (CRC) pathogenesis is largely unknown. The expression of GDH was determined by qPCR, western blot and immunohistochemistry in CRC cells and samples. The correlation of GDH expression with clinicopathologic features and prognosis was analyzed. The functional role of GDH in CRC cell proliferation, motility and metastasis was evaluated. We found that GDH was up-regulated both in colorectal cancer and metastatic lesions (n = 104). Patients with high GDH expression had poorer overall survival (HR 2.32; 95% CI 1.26-4.26; P = 0.007) and poorer disease-free survival rates (HR 2.48; 95% CI 1.25-4.92; P = 0.009) than those with low GDH expression. Furthermore, we showed that GDH expression was an independent prognostic factor for CRC. In addition, over-expression of GDH promoted cell proliferation, migration and invasion in vitro, whereas loss function of GDH did the opposite. Finally, we demonstrated that the promotion of CRC progression by GDH correlated with activation of STAT3 mediated epithelial-mesenchymal transition (EMT) induction. These results indicate that GDH plays a critical role in CRC progression, and may provide a novel metabolism therapeutic target for CRC treatment.