Oncotarget

Research Papers:

Kidney-type glutaminase (GLS1) is a biomarker for pathologic diagnosis and prognosis of hepatocellular carcinoma

Decai Yu, Xianbiao Shi, Gang Meng, Jun Chen, Chen Yan, Yong Jiang, Jiwu Wei _ and Yitao Ding

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Oncotarget. 2015; 6:7619-7631. https://doi.org/10.18632/oncotarget.3196

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Abstract

Decai Yu1,2,*, Xianbiao Shi1,*, Gang Meng2,4,*, Jun Chen3, Chen Yan5, Yong Jiang5, Jiwu Wei2,4, Yitao Ding1,2

1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China

2Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, China

3Department of Pathology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China

4Nanjing University Hightech Institute at Suzhou, Suzhou, 215123, China

5Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China

*These authors have contributed equally to this work

Correspondence to:

Jiwu Wei, e-mail: wjw@nju.edu.cn

Yitao Ding, e-mail: drdingyitao@sina.com.cn

Keywords: kidney-type glutaminase (GLS1), liver-type glutaminase (GLS2), hepatocellular carcinoma, biomarker

Received: December 30, 2014     Accepted: January 23, 2015     Published: March 26, 2015

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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