title: Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.
abstract: BACKGROUND
  Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.
  
  
  METHODS
  Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.
  
  
  RESULTS
  In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS.
  
  
  CONCLUSIONS
  We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway.
authors.forename: Marte
authors.initials: M
authors.lastname: Eilertsen
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.affiliation: Department of Medical Biology, University of Tromso, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: Department of Medical Biology, University of Tromso, Tromso, Norway; Department of Pharmacy, University of Tromso, Tromso, Norway.
authors.forename: Yury
authors.initials: Y
authors.lastname: Kiselev
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Stenvold
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway.
authors.forename: Ingvild
authors.initials: I
authors.lastname: Pettersen
authors.affiliation: Department of Medical Biology, University of Tromso, Tromso, Norway; Department of Pathology, Nordland Central Hospital, Bodo, Norway.
authors.forename: Khalid
authors.initials: K
authors.lastname: Al-Shibli
authors.affiliation: Department of Medical Biology, University of Tromso, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Richardsen
authors.affiliation: Department of Medical Biology, University of Tromso, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Clinical Medicine, University of Tromso, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D017154:Stromal Cells / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D014408:Biomarkers, Tumor; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C106260:SLC16A3 protein, human; C406962:SLC16A4 protein, human; C490427:SLC16A7 protein, human