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Higher autocrine motility factor/glucose-6-phosphate isomerase expression is associated with tumorigenesis and poorer prognosis in gastric cancer

Authors Ma YT, Xing XF, Dong B, Cheng XJ, Guo T, Du H, Wen XZ, Ji JF

Received 16 June 2018

Accepted for publication 6 August 2018

Published 25 October 2018 Volume 2018:10 Pages 4969—4980

DOI https://doi.org/10.2147/CMAR.S177441

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Yu-Teng Ma,1,2 Xiao-Fang Xing,1 Bin Dong,3 Xiao-Jing Cheng,1 Ting Guo,1 Hong Du,1 Xian-Zi Wen,1 Jia-Fu Ji1,2

1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Division of Gastrointestinal Cancer Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, China; 2Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China; 3Department of Pathology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China

Background: Glucose-6-phosphate isomerase (GPI) is a glycolytic-related enzyme that interconverts glucose-6-phosphate and fructose-6-phosphate in the cytoplasm. This protein is also secreted into the extracellular matrix by cancer cells and is, therefore, also called autocrine motility factor (AMF).
Methods: To clarify the roles of AMF/GPI in gastric cancer (GC), we collected 335 GC tissues and the corresponding adjacent noncancerous tissues, performed immunohistochemical studies, and analyzed the relationship between AMF/GPI expression and the patients’ clinicopathologic features.
Results: AMF/GPI expression was found to be significantly higher in the GC group than in the corresponding noncancerous tissue group (P<0.001). Additionally, AMF/GPI expression positively associated with a higher TNM stage and poorer prognosis in patients. Through Kaplan–Meier analysis and according to the Oncomine database, we found that AMF/GPI was overexpressed in GC tissues compared to normal mucosa, and the patients with higher AMF/GPI expression had poorer outcomes. We used AMF/GPI-silenced GC cell lines to observe how changes in AMP/GPI affect cellular phenotypes. AMF/GPI knockdown suppressed proliferation, migration, invasion, and glycolysis, and induced apoptosis in GC cells.
Conclusion:
These findings suggest that AMF/GPI overexpression is involved in carcinogenesis and promotes the aggressive phenotypes of GC cells.

Keywords: gastric cancer, glucose-6-phosphate isomerase, autocrine motility factor, tumorigenesis, prognosis, metabolism

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