J Cancer 2020; 11(1):83-91. doi:10.7150/jca.36495 This issue

Research Paper

Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

Xiaojia Liu1#, Xianxian Sui2#, Canjing Zhang3, Kelu Wei4, Yun Bao1, Ji Xiong1, Zhongwen Zhou1, Zhongqing Chen1, Chaoqun Wang5, Hongguang Zhu1,6, Feng Tang1✉

1. Division of Surgical Pathology, Huashan Hospital, Fudan University, Shanghai 200040, China
2. Laboratory of Medical Molecular Biology, Experimental Teaching Center, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
3. Key Laboratory of Medical Molecular Virology, the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
4. Shanghai Medical College, Fudan University, Shanghai 200032, China
5. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, 200040, China
6. Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
#These authors contributed equally to this work.

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Citation:
Liu X, Sui X, Zhang C, Wei K, Bao Y, Xiong J, Zhou Z, Chen Z, Wang C, Zhu H, Tang F. Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma. J Cancer 2020; 11(1):83-91. doi:10.7150/jca.36495. Available from https://www.jcancer.org/v11p0083.htm

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Abstract

Glutathione S-transferase (GST) family members play an important role in detoxification, metabolism and carcinogenesis. The aim of this study is to investigate the effect of Glutathione S-transferase A1 (GSTA1) on the prognosis of HCC and to understand its role in tumor progression and the possible mechanism. GSTA1 in HCC was assessed using immunohistochemical staining, and it was found that HCC patients with better pathological differentiation had higher GSTA1 abundance. Further, high GSTA1 expression was correlated with low AFP, absent PVTT, and early stage TNM for HCC patients. Higher GSTA1 indicated longer overall survival and disease-free survival, while lower GSTA1 indicated poorer prognosis. Subsequently, lentiviral vector carrying GSTA1 gene was successfully constructed and maintained high expression in 97H and SNU449 liver cancer cells. We found that high GSTA1 restrained liver cancer cell proliferation, migration and invasion in vitro. Western blot showed that LKB1 and p-AMPK were upregulated while p-mTOR, p-p70 S6 Kinase and MMP-9 were downregulated in high GSTA1 groups. Taken together, high GSTA1 correlated with satisfactory prognosis of HCC. Additionally, GSTA1 may act as a protective factor through suppression of tumorigenesis by targeting AMPK/mTOR in HCC.

Keywords: hepatocellular carcinomas, glutathione S-transferase A1 protein, prognosis, cellular proliferation, metastasis, AMP-Activated Protein Kinases