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Kidney-type Glutaminase (GLS1) is a Biomarker for Pathologic Diagnosis and Prognosis of Hepatocellular Carcinoma

Overview
Journal Oncotarget
Specialty Oncology
Date 2015 Apr 7
PMID 25844758
Citations 61
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Abstract

The lack of sensitive and specific biomarkers hinders pathological diagnosis and prognosis for hepatocellular carcinoma (HCC). Since glutaminolysis plays a crucial role in carcinogenesis and progression, we sought to determine if the expression of kidney-type and liver-type glutaminases (GLS1 and GLS2) were informative for pathological diagnosis and prognosis of HCC. We compared the expression of GLS1 and GLS2 in a large set of clinical samples including HCC, normal liver, and other liver diseases. We found that GLS1 was highly expressed in HCC; whereas, expression of GLS2 was mainly confined to non-tumor hepatocytes. The sensitivity and specificity of GLS1 for HCC were 96.51% and 75.21%, respectively. A metabolic switch from GLS2 to GLS1 was observed in a series of tissues representing progressive pathologic states mimicking HCC oncogenic transformation, including normal liver, fibrotic liver, dysplasia nodule, and HCC. We found that high expression of GLS1 and low expression of GLS2 in HCC correlated with survival time of HCC patients. Expression of GLS1 and GLS2 were independent indexes for survival time; however, prognosis was predominantly determined by the level of GLS1 expression. These findings indicate that GLS1 expression is a sensitive and specific biomarker for pathological diagnosis and prognosis of HCC.

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References
1.
Wang J, Erickson J, Fuji R, Ramachandran S, Gao P, Dinavahi R . Targeting mitochondrial glutaminase activity inhibits oncogenic transformation. Cancer Cell. 2010; 18(3):207-19. PMC: 3078749. DOI: 10.1016/j.ccr.2010.08.009. View

2.
Matsuno T . Bioenergetics of tumor cells: glutamine metabolism in tumor cell mitochondria. Int J Biochem. 1987; 19(4):303-7. DOI: 10.1016/0020-711x(87)90002-4. View

3.
Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

4.
Cassago A, Ferreira A, Ferreira I, Fornezari C, Gomes E, Greene K . Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism. Proc Natl Acad Sci U S A. 2012; 109(4):1092-7. PMC: 3268272. DOI: 10.1073/pnas.1112495109. View

5.
Yuneva M, Fan T, Allen T, Higashi R, Ferraris D, Tsukamoto T . The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type. Cell Metab. 2012; 15(2):157-70. PMC: 3282107. DOI: 10.1016/j.cmet.2011.12.015. View