Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

Shan,Yan-Shen; Hsu,Hui-Ping; Lai,Ming-Derg; Yen,Meng-Chi; Luo,Yi-Pey; Chen,Yi-Ling

doi:10.3892/or.2014.3556

Increased expression of argininosuccinate synthetase protein predicts poor prognosis in human gastric cancer

Authors:
- Yan-Shen Shan
- Hui-Ping Hsu
- Ming-Derg Lai
- Meng-Chi Yen
- Yi-Pey Luo
- Yi-Ling Chen
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Affiliations: Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C., Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C., Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C., Department of Senior Citizen Service Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, R.O.C.
Published online on: October 20, 2014 https://doi.org/10.3892/or.2014.3556
Pages: 49-57
Copyright: © Shan et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Aberrant expression of argininosuccinate synthetase (ASS1, also known as ASS) has been found in cancer cells and is involved in the carcinogenesis of gastric cancer. The aim of the present study was to investigate the level of ASS expression in human gastric cancer and to determine the possible correlations between ASS expression and clinicopathological findings. Immunohistochemistry was performed on paraffin‑embedded tissues to determine whether ASS was expressed in 11 of 11 specimens from patients with gastric cancer. The protein was localized primarily to the cytoplasm of cancer cells and normal epithelium. In the Oncomine cancer microarray database, expression of the ASS gene was significantly increased in gastric cancer tissues. To investigate the clinicopathological and prognostic roles of ASS expression, we performed western blot analysis of 35 matched specimens of gastric adenocarcinomas and normal tissue obtained from patients treated at the National Cheng Kung University Hospital. The ratio of relative ASS expression (expressed as the ASS/β-actin ratio) in tumor tissues to that in normal tissues was correlated with large tumor size (P=0.007) and with the tumor, node, metastasis (TNM) stage of the American Joint Committee on Cancer staging system (P=0.031). Patients whose cancer had increased the relative expression of ASS were positive for perineural invasion and had poor recurrence-free survival. In summary, ASS expression in gastric cancer was associated with a poor prognosis. Further study of mechanisms to silence the ASS gene or decrease the enzymatic activity of ASS protein has the potential to provide new treatments for patients with gastric cancer.

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