title: Metabolic phenotypes in pancreatic cancer.
abstract: BACKGROUND
  The aim of present study was to profile the glucose-dependent and glutamine- dependent metabolism in pancreatic cancer.
  
  
  METHODS
  We performed Immunohistochemical staining of GLUT1, CAIX, BNIP3, p62, LC3, GLUD1, and GOT1. Based on the expression of metabolism-related proteins, the metabolic phenotypes of tumors were classified into two categories, including glucose- and glutamine-dependent metabolism. There were Warburg type, reverse Warburg type, mixed type, and null type in glucose-dependent metabolism, and canonical type, non-canonical type, mixed type, null type in glutamine-dependent metabolism.
  
  
  RESULTS
  Longer overall survival was associated with high expression of BNIP3 in tumor (p = 0.010). Shorter overall survival was associated with high expression of GLUT1 in tumor (P = 0.002) and GOT1 in tumor (p = 0.030). Warburg type of glucose-dependent metabolism had a highest percentage of tumors with nerve infiltration (P = 0.0003), UICC stage (P = 0.0004), and activated autophagic status in tumor (P = 0.0167). Mixed type of glucose-dependent metabolism comprised the highest percentage of tumors with positive marginal status (P<0.0001), lymphatic invasion (P<0.0001), and activated autophagic status in stroma (P = 0.0002). Mixed type and Warburg type had a significant association with shorter overall survival (P = 0.018). Non-canonical type and mixed type of glutamine-dependent metabolism comprised the highest percentage of tumors with vascular invasion (p = 0.0073), highest percentage of activated autophagy in tumors (P = 0.0034). Moreover, these two types of glutamine-dependent metabolism were significantly associated with shorter overall survival (P<0.001). Further analysis suggested that most of tumors were dependent on both glucose- and glutamine-dependent metabolism. After dividing the tumors according to the number of metabolism, we found that the increasing numbers of metabolism subtypes inversely associated with survival outcome.
  
  
  CONCLUSIONS
  Warburg type, non-canonical type and mixed types of glucose- and glutamine-dependent metabolism comprised of more metabolically active, biologically aggressive and poor prognostic tumors. Moreover, the increasing subtypes and categories of the metabolism in each tumor significantly associated with poor prognosis.
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China; General Surgery Department, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Quanbo
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Langping
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zeng
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Li
authors.affiliation: General Surgery Department, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong Province, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Rufu
authors.initials: R
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D000071186:Beclin-1; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; C090121:BNIP3 protein, human; D000071186:Beclin-1; D051272:Glucose Transporter Type 1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C118585:P62 protein, human; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D005973:Glutamine; D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D005947:Glucose