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1.
Anticancer Res ; 44(8): 3321-3330, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39060044

RESUMO

BACKGROUND/AIM: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) is reportedly associated with the malignant potential of cancer. This study aimed to evaluate the association between FDG accumulation and tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: A prognostic analysis of data from 131 patients with PDAC who underwent FDG-PET/CT before curative-intent pancreatic surgery was performed. Capillary electrophoresis-mass spectrometry (CE-MS) was used to analyze the metabolome of tumor and non-neoplastic pancreas from 80 patients. These patients were divided into two groups: low SUVmax group (SUVmax <6.09) and high SUVmax group (SUVmax ≥6.09). RESULTS: Carbohydrate antigen 19-9 (CA19-9), maximum standardized uptake value (SUVmax) of PET, N stage, and postoperative chemotherapy were identified as significant prognostic factors by univariate analysis. SUVmax emerged as an independent prognostic factor for overall survival [hazard ratio (HR)=1.88, p<0.05] and disease-free survival (HR=2.01, p<0.05) in multivariate analysis. Metabolic analyses confirmed that 43 metabolites significantly differed depending on the accumulation of SUV in tumors. Metabolites involved in the removal of reactive oxygen species (e.g., hypotaurine, glutathione, Met), treatment resistance (UDP-N-acetylglucosamine), and proliferation (e.g., choline, leucine, isoleucine) were increased in the high SUVmax group. CONCLUSION: FDG accumulation is an important independent prognostic factor reflecting tumor activity associated with metabolic changes in cancer cells.


Assuntos
Carcinoma Ductal Pancreático , Fluordesoxiglucose F18 , Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Masculino , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Idoso , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Compostos Radiofarmacêuticos/metabolismo , Adulto , Idoso de 80 Anos ou mais
2.
Jpn J Clin Oncol ; 52(8): 887-895, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35523689

RESUMO

OBJECTIVE: We investigated the metabolic changes in pancreatic ductal adenocarcinoma to identify the mechanisms of treatment response of neoadjuvant chemoradiation therapy. METHODS: Frozen tumor and non-neoplastic pancreas tissues were prospectively obtained from 88 patients with pancreatic ductal adenocarcinoma who underwent curative-intent surgery. Sixty-two patients received neoadjuvant chemoradiation therapy and 26 patients did not receive neoadjuvant therapy (control group). Comprehensive analysis of metabolites in tumor and non-neoplastic pancreatic tissue was performed by capillary electrophoresis-mass spectrometry. RESULTS: Capillary electrophoresis-mass spectrometry detected 90 metabolites for analysis among more than 500 ionic metabolites quantified. There were significant differences in 27 tumor metabolites between the neoadjuvant chemoradiation therapy and control groups. There were significant differences in eight metabolites [1-MethylnNicotinamide, Carnitine, Glucose, Glutathione (red), N-acetylglucosamine 6-phosphate, N-acetylglucosamine 1-phosphate, UMP, Phosphocholine] between good responder and poor responder for neoadjuvant chemoradiation therapy. Among these metabolites, phosphocholine, Carnitine and Glutathione were associated with recurrence-free survival only in the neoadjuvant chemoradiation therapy group. Microarray confirmed marked gene suppression of choline transporters [CTL1-4 (SLC44A1-44A4)] in pancreatic ductal adenocarcinoma tissue of neoadjuvant chemoradiation therapy group. CONCLUSION: The present study identifies several important metabolic consequences and potential neoadjuvant chemoradiation therapy targets in pancreatic ductal adenocarcinoma. Choline metabolism is one of the key pathways involved in recurrence of the patients with pancreatic ductal adenocarcinoma who received neoadjuvant chemoradiation therapy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Antígenos CD , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Carnitina , Quimiorradioterapia , Glutationa , Humanos , Terapia Neoadjuvante , Recidiva Local de Neoplasia/diagnóstico , Proteínas de Transporte de Cátions Orgânicos , Pancreatectomia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Fosforilcolina , Neoplasias Pancreáticas
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