Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance

Cao,Jun; Zhang,Chi; Jiang,Guo‑Qing; Jin,Sheng‑Jie; Gao,Zhi‑Hui; Wang,Qian; Yu,De‑Cai; Ke,Ai‑Wu; Fan,Yi‑Qun; Li,Da‑Wei; Wang,Ao‑Qing; Bai,Dou‑Sheng

doi:10.3892/mmr.2019.10399

Expression of GLS1 in intrahepatic cholangiocarcinoma and its clinical significance

Authors:
- Jun Cao
- Chi Zhang
- Guo‑Qing Jiang
- Sheng‑Jie Jin
- Zhi‑Hui Gao
- Qian Wang
- De‑Cai Yu
- Ai‑Wu Ke
- Yi‑Qun Fan
- Da‑Wei Li
- Ao‑Qing Wang
- Dou‑Sheng Bai
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Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China, Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu 225000, P.R. China, Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210093, P.R. China, Liver Cancer Institute, Ministry of Education, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Shanghai 200032, P.R. China, Department of Surgery, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: June 19, 2019 https://doi.org/10.3892/mmr.2019.10399
Pages: 1915-1924

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Abstract

Kidney‑type glutaminase (GLS1) plays a significant role in tumor metabolism. Our recent studies demonstrated that GLS1 was aberrantly expressed in hepatocellular carcinoma (HCC) and facilitated tumor progression. However, the roles of GLS1 in intrahepatic cholangiocarcinoma (ICC) remain largely unknown. Thus, the aim of this study was to evaluate the expression and clinical significance of GLS1 in ICC. For this purpose, combined data from the Oncomine database with those of immunohistochemistry were used to determine the expression levels of GLS1 in cancerous and non‑cancerous tissues. Second, a wound‑healing assay and Transwell assay were used to observe the effects of the knockdown and overexpression of GLS1 on the invasion and migration of ICC cells. We examined the associations between the expression of GLS1 and epithelial‑mesenchymal transition (EMT)‑related markers by western blot analysis. Finally, we examined the associations between GLS1 levels and clinicopathological factors or patient prognosis. The results revealed that GLS1 was overexpressed in different digestive system tumors, including ICC, and that GLS1 expression in ICC tissue was higher than that in peritumoral tissue. The overexpression of GLS1 in RBE cells induced metastasis and invasion. Moreover, the EMT‑related markers, E‑cadherin and Vimentin, were regulated by GLS1 in ICC cells. By contrast, the knockdown of GLS1 expression in QBC939 cells yielded opposite results. Clinically, a high expression of GLS1 in ICC samples negatively correlated with E‑cadherin expression and positively correlated with Vimentin expression. GLS1 protein expression was associated with tumor differentiation (P=0.001) and lymphatic metastasis (P=0.029). Importantly, patients with a high GLS1 expression had a poorer overall survival (OS) and a shorter time to recurrence than patients with a low GLS1 expression. Multivariate analysis indicated that GLS1 expression was an independent prognostic indicator. On the whole, the findings of this study demonstrated that GLS1 is an independent prognostic biomarker of ICC. GLS1 facilitates ICC progression and may thus prove to be a therapeutic target in ICC.

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