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

Abstract

// Decai Yu 1, 2, * , Xianbiao Shi 1, * , Gang Meng 2, 4, * , Jun Chen 3 , Chen Yan 5 , Yong Jiang 5 , Jiwu Wei 2, 4 , Yitao Ding 1, 2 1 Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China 2 Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, 210093, China 3 Department of Pathology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210093, China 4 Nanjing University Hightech Institute at Suzhou, Suzhou, 215123, China 5 Department 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.