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12-lipoxygenase promotes tumor progress by TGF-β1-mediated epithelial to mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma

Authors Qu Y, Wen Z, Mi S, Chen P, Wang J, Jia Y, Cheng Y

Received 16 April 2019

Accepted for publication 25 August 2019

Published 11 September 2019 Volume 2019:11 Pages 8303—8313

DOI https://doi.org/10.2147/CMAR.S212478

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava


Yan Qu,* Zhihua Wen,* Si Mi, Pengxiang Chen, Jianbo Wang, Yibin Jia, Yufeng Cheng

Department of Radiation Oncology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yufeng Cheng
Department of Radiation Oncology, Qilu Hospital of Shandong University, 107 West Wenhua Road, Jinan, 250012, People’s Republic of China
Tel +86 1 876 978 5399
Email qlchengyf@163.com

Purpose: To clarify the effect of 12-lipoxygenase/12-hydroxyeicosatetraeonic acid (12-LOX/12-HETE) on progress of esophageal squamous cell carcinoma (ESCC) and the possible mechanism.
Patients and methods: We performed cell experiments including chemical treatment, transfection, Western blotting and transwell assay to investigate the function of 12-LOX/12-HETE. Slices of tumor tissues were obtained from ESCC patients treated in Qilu Hospital of Shandong University. Immunohistochemical (IHC) staining was done to find their correlation with prognosis and clinicopathological characteristics.
Results: In ESCC cells, inhibition of 12-LOX caused a decrease in transforming growth factor-β1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) level, and abilities of migration and invasion were also inhibited. Nevertheless, the inhibition could be partly relieved when treated with 12-HETE or TGF-β1. Analyses of IHC staining indicated a positive correlation between the expression of 12-LOX and EMT level, and an inverse correlation between 12-LOX and overall survival (OS). Univariate and multivariate analyses further suggested that 12-LOX was an independent prognostic factor for ESCC patients.
Conclusion: In conclusion, our study proved that 12-LOX/12-HETE-promoted tumor migration and invasion might partly be through TGF-β1-mediated EMT in ESCC, and 12-LOX could be a promising biomarker for predicting prognosis in ESCC patients.

Keywords: 12-LOX, 12-HETE, Baicalein, tumor metastasis, overall survival

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