Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation.
BMC Cancer
; 22(1): 289, 2022 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-35300626
ABSTRACT
BACKGROUND:
Pheochromocytomas (PCC) and paragangliomas (PGL) are catecholamine-producing neuroendocrine tumors. According to the World Health Organization Classification 2017, all PCC/PGL are considered to have malignant potential. There is growing evidence that PCC/PGL represent a metabolic disease that leads to aerobic glycolysis. Cellular energy metabolism involves both transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and succinate dehydrogenase (SDH) subtypes, but the association of these substances with PCC/PGL is largely unknown.METHODS:
We investigated SDHB gene mutation and protein expressions for SDHB and Nrf2 in surgical specimens from 29 PCC/PGL. We also assessed preoperative maximum standard glucose uptake (SUVmax) on [18F]fluorodeoxy-glucose positron emission tomography and mRNA levels for Nrf2.RESULTS:
Among 5 PCC/PGL with a PASS Score ≥ 4 or with a moderately to poorly differentiated type in the GAPP Score, 4 were metastatic and found to be SDHB mutants with homogeneous deletion of SDHB protein. SDHB mutants showed a higher expression of Nrf2 protein and a higher preoperative SUVmax than non-SDHB mutants with a PASS < 4 or a well-differentiated GAPP type. Furthermore, protein expression of Nrf2 was positively associated with preoperative SUVmax. The Nrf2 mRNA level positively correlated with malignant phenotype, higher expression for Nrf2 protein and SDHB gene mutant, but negatively correlated with expression for SDHB protein. There was also a positive correlation between Nrf2 mRNA level and SUVmax.CONCLUSION:
These results suggest that activation of Nrf2 and elevated metabolism play roles in PCC/PGL with malignant potential that have SDHB gene mutation and SDHB deficiency.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Paraganglioma
/
Feocromocitoma
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Succinato Desidrogenase
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Neoplasias das Glândulas Suprarrenais
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Fator 2 Relacionado a NF-E2
/
Glucose
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
BMC Cancer
Ano de publicação:
2022
Tipo de documento:
Article