title: Prognostic significance of monocarboxylate transporter expression in oral cavity tumors.
abstract: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common type of cancer. The majority of patients present advanced stage disease and has poor survival. Therefore, it is imperative to search for new biomarkers and new alternative and effective treatment options. Most cancer cells rely on aerobic glycolysis to generate energy and metabolic intermediates. This phenotype is a hallmark of cancer, characterized by an increase in glucose consumption and production of high amounts of lactate. Consequently, cancer cells need to up-regulate many proteins and enzymes related with the glycolytic metabolism. Thus, the aim of this study was to characterize metabolic phenotype of oral cavity cancers (OCC) by assessing the expression pattern of monocarboxylate transporters (MCTs) 1, 2 and 4 and other proteins related with the glycolytic phenotype.
  
  
  
  We evaluated the immunohistochemical expression of MCT1, MCT4, CD147, GLUT1 and CAIX in 135 human samples of OCC and investigated the correlation with clinicopathological parameters and the possible association with prognosis.
  
  
  
  We observed that all proteins analyzed presented significantly higher plasma membrane expression in neoplastic compared to non-neoplastic samples. MCT4 was significantly associated with T-stage and advanced tumoral stage, while CD147 was significantly correlated with histologic differentiation. Interestingly, tumors expressing both MCT1 and MCT4 but negative for MCT2 were associated with shorter overall survival.
  
  
  
  Overexpression of MCT1/4, CD147, GLUT1 and CAIX, supports previous findings of metabolic reprograming in OCC, warranting future studies to explore the hyper-glycolytic phenotype of these tumors. Importantly, MCT expression revealed to have a prognostic value in OCC survival.
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Simões-Sousa
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Granja
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.|c Barretos School of Health Sciences Dr. Paulo Prata - FACISB , Barretos , Sao Paulo , Brazil.|d Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.
authors.forename: Céline
authors.initials: C
authors.lastname: Pinheiro
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Fernandes
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.|d Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.|e Laboratory of Medical Investigation (LIM-14), Faculdade de Medicina da Universidade de , São Paulo , Brazil.
authors.forename: Adhemar
authors.initials: A
authors.lastname: Longatto-Filho
authors.affiliation: d Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Laus
authors.affiliation: f Head and Neck Surgery Department , Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.
authors.forename: Cira Danielle Casado
authors.initials: CD
authors.lastname: Alves
authors.affiliation: g Department of Pathology and Forensic Sciences , University Hospital and School of Medicine of Santiago de Compostela, Santiago de Compostela , A Coruña , Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Suárez-Peñaranda
authors.affiliation: h Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Health Research Institute of Santiago (IDIS), Santiago de Compostela , A Coruña , Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Pérez-Sayáns
authors.affiliation: d Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.|f Head and Neck Surgery Department , Barretos Cancer Hospital , Barretos , Sao Paulo , Brazil.
authors.forename: Andre
authors.initials: A
authors.lastname: Lopes Carvalho
authors.affiliation: i IPATIMUP - Institute of Molecular Pathology and Immunology of University of Porto , Porto , Portugal.|j Medical Faculty of the University of Porto , Porto , Portugal.|k Department of Pathology and Medicine , Laboratoire National de Sante , Dudelange , Luxembourg.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.affiliation: h Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry, Health Research Institute of Santiago (IDIS), Santiago de Compostela , A Coruña , Spain.
authors.forename: Abel
authors.initials: A
authors.lastname: García-García
authors.affiliation: a Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|b ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
authors.forename: Fatima
authors.initials: F
authors.lastname: Baltazar
mesh_terms: D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009055:Mouth / Q000378:metabolism / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis
chemical_list: D027501:Monocarboxylic Acid Transporters
keywords: aerobic glycolysis; head and neck cancer; lactate transport; monocarboxylate transporters