3 results on '"Echizenya, Sumire"'
Search Results
2. Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18F-Fluoromisonidazole and 18F-Fluorodeoxyglucose Positron Emission Tomography.
- Author
-
Okamoto, Michinari, Yamaguchi, Shigeru, Sawaya, Ryosuke, Echizenya, Sumire, Ishi, Yukitomo, Kaneko, Sadahiro, Motegi, Hiroaki, Toyonaga, Takuya, Hirata, Kenji, and Fujimura, Miki
- Subjects
GLUCOSE metabolism ,STAINS & staining (Microscopy) ,GENETIC mutation ,GLIOMAS ,PHOSPHATASES ,METABOLISM ,IMIDAZOLES ,CANCER patients ,QUALITATIVE research ,COMPARATIVE studies ,RADIOPHARMACEUTICALS ,POSITRON emission tomography ,GENE expression profiling ,FLUORESCENT antibody technique ,MESSENGER RNA ,DESCRIPTIVE statistics ,RESEARCH funding ,CEREBRAL anoxia ,DEOXY sugars ,CELL lines ,TUMOR markers ,OVERALL survival ,MEDICAL logic - Abstract
Purpose. Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (
18 F-FMISO) and fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism. Methods. Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma (n = 33) who underwent preoperative18 F-FMISO and18 F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort (n = 17) and validated by The Cancer Genome Atlas (TCGA) database (n = 167). Results. Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 (G6PC3) correlated with18 F-FDG LNR (P = 0.03). In addition, G6PC3 mRNA expression in18 F-FMISO high-accumulated glioblastomas was significantly higher than that in18 F-FMISO low-accumulated glioblastomas (P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database. Conclusion. G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high18 F-FDG and18 F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma. [ABSTRACT FROM AUTHOR]- Published
- 2024
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3. Identifying G6PC3 as a Potential Key Molecule in Hypoxic Glucose Metabolism of Glioblastoma Derived from the Depiction of 18 F-Fluoromisonidazole and 18 F-Fluorodeoxyglucose Positron Emission Tomography.
- Author
-
Okamoto M, Yamaguchi S, Sawaya R, Echizenya S, Ishi Y, Kaneko S, Motegi H, Toyonaga T, Hirata K, and Fujimura M
- Subjects
- Humans, Fluorodeoxyglucose F18, Tomography, X-Ray Computed, Positron-Emission Tomography, Glucose, Hypoxia, RNA, Messenger, Glucose-6-Phosphatase, Glioblastoma diagnostic imaging, Glioblastoma genetics, Fluorine Radioisotopes, Misonidazole analogs & derivatives
- Abstract
Purpose: Glioblastoma is the most aggressive primary brain tumor, characterized by its distinctive intratumoral hypoxia. Sequential preoperative examinations using fluorine-18-fluoromisonidazole (
18 F-FMISO) and fluorine-18-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) could depict the degree of glucose metabolism with hypoxic condition. However, molecular mechanism of glucose metabolism under hypoxia in glioblastoma has been unclear. The aim of this study was to identify the key molecules of hypoxic glucose metabolism., Methods: Using surgically obtained specimens, gene expressions associated with glucose metabolism were analyzed in patients with glioblastoma ( n = 33) who underwent preoperative18 F-FMISO and18 F-FDG PET to identify affected molecules according to hypoxic condition. Tumor in vivo metabolic activities were semiquantitatively evaluated by lesion-normal tissue ratio (LNR). Protein expression was confirmed by immunofluorescence staining. To evaluate prognostic value, relationship between gene expression and overall survival was explored in another independent nonoverlapping clinical cohort ( n = 17) and validated by The Cancer Genome Atlas (TCGA) database ( n = 167)., Results: Among the genes involving glucose metabolic pathway, mRNA expression of glucose-6-phosphatase 3 ( G6PC3 ) correlated with18 F-FDG LNR ( P = 0.03). In addition, G6PC3 mRNA expression in18 F-FMISO high-accumulated glioblastomas was significantly higher than that in18 F-FMISO low-accumulated glioblastomas ( P < 0.01). Protein expression of G6PC3 was consistent with mRNA expression, which was confirmed by immunofluorescence analysis. These findings indicated that the G6PC3 expression might be facilitated by hypoxic condition in glioblastomas. Next, we investigated the clinical relevance of G6PC3 in terms of prognosis. Among the glioblastoma patients who received gross total resection, mRNA expressions of G6PC3 in the patients with poor prognosis (less than 1-year survival) were significantly higher than that in the patients who survive more than 3 years. Moreover, high mRNA expression of G6PC3 was associated with poor overall survival in glioblastoma, as validated by TCGA database., Conclusion: G6PC3 was affluently expressed in glioblastoma tissues with coincidentally high18 F-FDG and18 F-FMISO accumulation. Further, it might work as a prognostic biomarker of glioblastoma. Therefore, G6PC3 is a potential key molecule of glucose metabolism under hypoxia in glioblastoma., Competing Interests: The authors have no relevant financial or nonfinancial interests to disclose., (Copyright © 2024 Michinari Okamoto et al.)- Published
- 2024
- Full Text
- View/download PDF
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