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Warburg effect in tumor bearing dogs
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Abstract(s)
Tal como em medicina humana, a frequência de cancros apresenta uma tendência crescente nos animais de
companhia, e apesar dos recentes avanços no diagnóstico e tratamento, continua a ser uma das principais
causas de morbilidade e mortalidade em cães e gatos. A descoberta de novos biomarcadores clinicamente
úteis para triagem, diagnóstico, detecção precoce da progressão e prognóstico de doenças oncológicas, bem
como a descrição de vias metabólicas que poderão ser potenciais alvos terapêuticos são de extrema
importância em oncologia humana e veterinária.
O efeito Warburg descreve a síntese de ATP por células tumorais através de uma via metabólica alternativa à
fosforilação oxidativa, a glicólise aeróbica, mesmo em condições de normoxemia. A glicólise aeróbia poderá
produzir alterações bioquímicas que podem ser utilizadas como biomarcadores clínicos.
Na medicina humana, este fenómeno tem sido documentado em numerosos estudos em oncologia. No
entanto, a informação relacionada com o efeito Warburg em oncologia veterinária é escassa. Por este motivo,
este estudo visou investigar as alterações no metabolismo energético tumoral através do estudo das
variações metabólicas associadas ao efeito Warburg, através da determinação da concentração sérica de
glucose, fructosamina, lactato e lactato desidrogenase (LDH) em cães com diferentes neoplasias malignas.
Foram avaliados neste estudo 36 cães diagnosticados com diferentes tumores malignos e em diferentes
estadios clínicos (grupo de animais doentes) e 23 cães considerados saudáveis, que constituíram o grupo
controlo. Os animais doentes apresentaram concentrações séricas de lactato e LDH significativamente
superiores (P=0.009 e P=0.023, respetivamente), e de fructosamina significativamente inferiores aos animais
do grupo controlo (P=0.007). As concentrações séricas de glucose foram também inferiores em cães com
neoplasias do que nos cães saudáveis, mas as diferenças não foram significativas (P=0.174). Os cães
doentes foram divididos em grupos de acordo com o tipo de tumor que apresentaram, nomeadamente nos
grupos de cães com carcinoma (n=13), sarcoma (n=10), linfoma (n=8) e adenocarcinoma mamário (n=8).
Não foram encontradas diferenças significativas nas concentrações séricas de glucose, fructosamina, lactato
e lactato desidrogenase entre estes grupos, ou entre estes grupos e os animais saudáveis (P>0.05 em todos
os casos).
Os resultados obtidos neste estudo mostram a ocorrência de alterações metabólicas que poderão estar
associadas ao efeito Warburg em cães com diferentes tumores malignos, sugerindo que a glicólise aeróbica
pode estar implicada na carcinogénese de diferentes neoplasias caninas. Os resultados sugerem também
que os metabolitos analisados, nomeadamente a fructosamina, o lactato e a LDH, poderão ser
biomarcadores úteis na prática clínica para triagem, diagnóstico, detecção precoce da progressão e
prognóstico de doenças oncológicas caninas. Sugerem ainda que as vias metabólicas implicadas no efeito
Warburg poderão ser potenciais alvos terapêuticos de diferentes neoplasias caninas. No entanto, neste
estudo foi analisado um grupo pequeno de animais, e com tumores diferentes e em diferentes estadios
clínicos. Serão necessários estudos futuros, com um maior número de animais e com uma população mais
homogénea, para avaliar a função biológica do efeito Warburg na carcinogénese e a sua aplicação clínica em
cada tipo tumoral.
As in human medicine, the frequency of cancer presents an increasing trend in companion animals, and despite recent advances in diagnosis and treatment, remains a major cause of morbidity and mortality in dogs and cats. The discovery of new clinically useful biomarkers for screening, diagnosis, early detection of progression and prognosis of oncological diseases, as well as the description of metabolic pathways that could be potential therapeutic targets are of extreme importance in human and veterinary oncology. The Warburg effect describes the synthesis of ATP by tumor cells through an alternative metabolic pathway to oxidative phosphorylation, the aerobic glycolysis, even under normoxemia conditions. Aerobic glycolysis may produce biochemical changes that can be used as clinical biomarkers. In human medicine, this phenomenon has been documented in numerous studies in oncology. However, information related to the Warburg effect in veterinary oncology is scarce. For this reason, this study aimed to investigate changes in tumor energy metabolism through the study of metabolic variations associated with the Warburg effect, by determining the serum concentration of glucose, fructosamine, lactate and lactate dehydrogenase (LDH) in dogs with different malignant neoplasms. In this study, 36 dogs diagnosed with different malignant tumors and in different clinical stages (group of diseased animals) and 23 dogs considered healthy, which constituted the control group, were evaluated. Diseased animals (n=36) had significantly higher serum lactate and LDH concentrations (P=0.009 and P=0.023, respectively), and significantly lower serum fructosamine than animals in the control group (P=0.007). Serum glucose concentrations were also lower in dogs with cancer than in healthy dogs, but the differences were not significant (P=0.174). The diseased dogs were divided into groups according to the type of tumor, namely in the groups of dogs with carcinoma (n=13), sarcoma (n=10), lymphoma (n=8) and mammary adenocarcinoma (n=8). No significant differences were found in the serum concentrations of glucose, fructosamine, lactate and LDH between these groups, or between these groups and healthy animals (P>0.05 in all cases). The results obtained in this study show the occurrence of metabolic alterations that may be associated with the Warburg effect in dogs with different malignant tumors, suggesting that aerobic glycolysis may be involved in the carcinogenesis of different canine neoplasms. The results also suggest that the analyzed metabolites, namely fructosamine, lactate and LDH, might be useful biomarkers in clinical practice for screening, diagnosis, early detection of progression and prognosis of canine oncological diseases. They also suggest that the metabolic pathways involved in the Warburg effect might be potential therapeutic targets for different canine neoplasms. However, this study analyzed a small group of animals, with different tumors and at different clinical stages. Future studies, with a greater number of animals and with a more homogeneous population, will be necessary to evaluate the biological role of the Warburg effect in carcinogenesis and its clinical application in specific tumor types
As in human medicine, the frequency of cancer presents an increasing trend in companion animals, and despite recent advances in diagnosis and treatment, remains a major cause of morbidity and mortality in dogs and cats. The discovery of new clinically useful biomarkers for screening, diagnosis, early detection of progression and prognosis of oncological diseases, as well as the description of metabolic pathways that could be potential therapeutic targets are of extreme importance in human and veterinary oncology. The Warburg effect describes the synthesis of ATP by tumor cells through an alternative metabolic pathway to oxidative phosphorylation, the aerobic glycolysis, even under normoxemia conditions. Aerobic glycolysis may produce biochemical changes that can be used as clinical biomarkers. In human medicine, this phenomenon has been documented in numerous studies in oncology. However, information related to the Warburg effect in veterinary oncology is scarce. For this reason, this study aimed to investigate changes in tumor energy metabolism through the study of metabolic variations associated with the Warburg effect, by determining the serum concentration of glucose, fructosamine, lactate and lactate dehydrogenase (LDH) in dogs with different malignant neoplasms. In this study, 36 dogs diagnosed with different malignant tumors and in different clinical stages (group of diseased animals) and 23 dogs considered healthy, which constituted the control group, were evaluated. Diseased animals (n=36) had significantly higher serum lactate and LDH concentrations (P=0.009 and P=0.023, respectively), and significantly lower serum fructosamine than animals in the control group (P=0.007). Serum glucose concentrations were also lower in dogs with cancer than in healthy dogs, but the differences were not significant (P=0.174). The diseased dogs were divided into groups according to the type of tumor, namely in the groups of dogs with carcinoma (n=13), sarcoma (n=10), lymphoma (n=8) and mammary adenocarcinoma (n=8). No significant differences were found in the serum concentrations of glucose, fructosamine, lactate and LDH between these groups, or between these groups and healthy animals (P>0.05 in all cases). The results obtained in this study show the occurrence of metabolic alterations that may be associated with the Warburg effect in dogs with different malignant tumors, suggesting that aerobic glycolysis may be involved in the carcinogenesis of different canine neoplasms. The results also suggest that the analyzed metabolites, namely fructosamine, lactate and LDH, might be useful biomarkers in clinical practice for screening, diagnosis, early detection of progression and prognosis of canine oncological diseases. They also suggest that the metabolic pathways involved in the Warburg effect might be potential therapeutic targets for different canine neoplasms. However, this study analyzed a small group of animals, with different tumors and at different clinical stages. Future studies, with a greater number of animals and with a more homogeneous population, will be necessary to evaluate the biological role of the Warburg effect in carcinogenesis and its clinical application in specific tumor types
Description
Keywords
Canino Efeito Warburg Fructosamina Glucose Lactato Lactato desidrogenase Neoplasia Canine Fructosamine Lactate Lactate Lactate dehydrogenase Neoplasia Warburg effect