title: Glutamate dehydrogenase is a novel prognostic marker and predicts metastases in colorectal cancer patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These results indicate that GDH plays a critical role in CRC progression, and may provide a novel metabolism therapeutic target for CRC treatment.
authors.affiliation: Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. liugaojie2014@163.com.|Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. liugaojie2014@163.com.
authors.forename: Gaojie
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Emergency Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. zhujie2010@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Emergency Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. mengleiyy23j@163.com.
authors.forename: Menglei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, Qingyuan People's Hospital, The sixth affiliated hospital of Guangzhou Medical University, Guangdong, 511518, China. canfengccc2@163.com.
authors.forename: Canfeng
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authors.lastname: Cai
authors.affiliation: Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. zhouyu2013@163.com.|Department of Pancreaticobiliary Surgery, Guangdong Academy of Medical Sciences and Guangdong General Hospital, Guangzhou, 510120, China. zhouyu2013@163.com.
authors.forename: Yu
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authors.lastname: Zhou
authors.affiliation: Department of Pancreaticobiliary Surgery, Guangdong Academy of Medical Sciences and Guangdong General Hospital, Guangzhou, 510120, China. yumin2013@163.com.
authors.forename: Min
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authors.affiliation: Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. fuzhiqiang2010@163.com.
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authors.affiliation: Department of Hepatobiliary Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, 510120, China. medoctor2013@126.com.
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authors.affiliation: Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. yangbing2000@126.com.
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authors.affiliation: Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. liyingru2007@126.com.
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authors.affiliation: Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. gzhorses1995@126.com.
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authors.affiliation: Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. huizhaoxx@163.com.
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authors.affiliation: Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. zhihuali2002@163.com.
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authors.affiliation: Department of Gastrointestinal Surgery, Qingyuan People's Hospital, The sixth affiliated hospital of Guangzhou Medical University, Guangdong, 511518, China. chaomingtt001@163.com.
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authors.affiliation: Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. zengbing2007@163.com.|Department of Gastrointestinal Surgery, Qingyuan People's Hospital, The sixth affiliated hospital of Guangzhou Medical University, Guangdong, 511518, China. zengbing2007@163.com.|Department of Pancreaticobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, 510120, China. zengbing2007@163.com.
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mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005969:Glutamate Dehydrogenase / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D016016:Proportional Hazards Models; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D005973:Glutamine; D005969:Glutamate Dehydrogenase