Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma
Abstract
Background/aims Glutamine synthetase (GS) catalyzes the synthesis of glutamine, a major energy source of cells, and is upregulated in a subset of human hepatocellular carcinomas (HCCs). GS expression may be related to tumor recurrence, since GS-expressing tumors have a growth advantage in that they are independent of the extracellular glutamine supply. However, there are no studies concerning the prognostic value of GS expression in patients with HCC.Methods Seventy-three patients with a single advanced HCC nodule who underwent curative hepatectomy were included in the study. GS expression in the HCC nodules was analyzed immunohistochemically and was compared with clinicopathologic features and the behavior of the tumors. Survival curves were assessed according to the Kaplan-Meier product-limit method and multivariate analysis based on the Cox regression model was performed.Results GS expression was strong in 26 cases (35.6%, high-GS group) and weak or absent in 47 cases (64.4%, low-GS group). Univariate analysis showed that the high-GS group had a significantly shorter disease-free survival time than the low-GS group (p=0.042). Multivariate analysis revealed that GS expression (p=0.021), as well as Child's classification (p=0.005) and portal invasion (p=0.039), was a significant and independent prognostic parameter that affected tumor recurrence.Conclusion The results of this study indicate that GS expression may enhance the metastatic potential in HCC, and GS immunostaining may be helpful in identifying HCC patients at high risk for disease recurrence.
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Glutamine synthetase is overexpressed in some cancers.
“Glutamine synthetase (GS) has been found to be overexpressed in some cancers (Osada et al., 2000);”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Osada et al., 2000
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- Authors
- Osada, T., Nagashima, I., Tsuno, N. H., Kitayama, J., & Nagawa, H.
- Affiliations
- The University of Tokyo (JP)
- Teikyo University (JP)
- Corresponding author
- Osada, Takuya
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 33
- Issue
- 2
- Pages
- 247-253
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2110379988
- Cited by
- 55
- References
- 38
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 1 · 2013: 3
- FWCI
- 0.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- glutamine synthetase, hepatocellular carcinoma, prognostic factors, tumor recurrence, disease-free survival, hepatectomy, Child-Pugh score, portal vein invasion, glutamine metabolism, metastatic potential
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Glutamate-Ammonia Ligase, Carcinoma, Hepatocellular, Humans, Liver Neoplasms, Male, Middle Aged, Prognosis, Biomarkers, Tumor, Survival Analysis
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