The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.
BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.
a Barretos School of Health Sciences, Dr. Paulo Prata - FACISB , Barretos , São Paulo , Brazil.|b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Céline
C
Pinheiro
c Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|d ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
Vera
V
Miranda-Gonçalves
b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.|c Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|d ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.|e Laboratory of Medical Investigation (LIM-14), School of Medicine, University of São Paulo , São Paulo , Brazil.
Adhemar
A
Longatto-Filho
b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Anna L S A
AL
Vicente
b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Gustavo N
GN
Berardinelli
f Pathology Department , Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Cristovam
C
Scapulatempo-Neto
a Barretos School of Health Sciences, Dr. Paulo Prata - FACISB , Barretos , São Paulo , Brazil.
Ricardo F A
RF
Costa
f Pathology Department , Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Cristiano R
CR
Viana
b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.|c Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|d ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
Rui M
RM
Reis
c Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho , Braga , Portugal.|d ICVS/3B's-PT Government Associate Laboratory , Braga/Guimarães , Portugal.
Fátima
F
Baltazar
b Molecular Oncology Research Center, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.|g Surgery Department , Melanoma/Sarcoma, Barretos Cancer Hospital , Barretos , São Paulo , Brazil.
Vinicius L
VL
Vazquez
D000328:Adult; D000368:Aged; D000071231:Carbonic Anhydrase IX / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009506:Nevus / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D027981:Symporters / Q000235:genetics* / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
D000071231:Carbonic Anhydrase IX; D020558:GTP Phosphohydrolases; D051272:Glucose Transporter Type 1; D008565:Membrane Proteins; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D048493:Proto-Oncogene Proteins B-raf; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C406962:SLC16A4 protein, human; C495677:SLC2A1 protein, human; C482119:BRAF protein, human; C579846:NRAS protein, human
Cancer; Warburg effect; glycolysis; melanoma; monocarboxylate transporters