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Overexpression of ST3Gal-I promotes migration and invasion of HCCLM3 in vitro and poor prognosis in human hepatocellular carcinoma

Authors Wu H, Shi X, Zhang H, Song Q, Yang X, Hu W, Mei G, Chen X, Mao Q, Chen Z

Received 16 September 2015

Accepted for publication 28 January 2016

Published 18 April 2016 Volume 2016:9 Pages 2227—2236

DOI https://doi.org/10.2147/OTT.S96510

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 5

Editor who approved publication: Dr Faris Farassati


Han Wu,1,* Xue-Liang Shi,1,* Hai-Jian Zhang,2 Qing-Jie Song,1 Xiao-Bing Yang,1 Wei-Dong Hu,1 Guang-Lin Mei,1 Xi Chen,1 Qin-Sheng Mao,1 Zhong Chen1

1Department of General Surgery, The Affiliated Hospital of Nantong University, 2Research Center of Clinical Medicine, The Affiliated Hospital of Nantong University, Nantong, People’s Republic of China

*These authors contributed equally to this work


Purpose: Excessive ST3Gal-I levels predict a poor outcome for patients with several types of tumors. This study aims to investigate the role of ST3Gal-I in determining the invasive and metastatic potential of human hepatocellular carcinoma (HCC) and clinical prognosis for patients with HCC.
Methods: We compared the expression of ST3Gal-I in various HCC cell lines and in 20 pairs of tumor and peritumor tissue samples using Western blot analysis. Changes in the degree of invasiveness and migration were determined before and after small interfering RNA-induced knockdown of ST3Gal-I using a Transwell matrigel invasion assay and scratch wound assay. The correlation between ST3Gal-I expression and prognosis was determined in a large HCC patient cohort (n=273).
Results: ST3Gal-I expression was higher in metastatic HCCLM3 cells and tumor tissue compared with normal adjacent tissue. Following the ST3Gal-I knockdown, the invasiveness and migration of HCCLM3 cells were markedly reduced. ST3Gal-I expression in HCC correlated closely with tumor thrombus (P<0.001), tumor size (>5.0 cm, P=0.032), tumor node metastasis stages II–III (P=0.002), and Barcelona Clinic Liver Cancer stages B–C (P<0.001). Cox regression analysis demonstrated that ST3Gal-I is an independent predictor of prognosis in patients with HCC, and related to disease-free survival (hazard ratio =1.464, P=0.037) and overall survival (hazard ratio =1.662, P=0.012).
Conclusion: ST3Gal-I might contribute to the invasiveness and metastatic nature of HCC and, thus, could be an independent predictor of recurrence and a suitable pharmaceutical target in patients with HCC.

Keywords: ST3Gal-I, hepatocellular carcinoma, sialyltransferase, prognosis, tumor progression

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