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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression
Li-Ping Liu, Xi-Ping Sheng, Tian-Kui Shuai, Yong-Xun Zhao, Bin Li, Yu-Min Li
Li-Ping Liu, The Second Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China
Li-Ping Liu, Bin Li, Department of Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Li-Ping Liu, Tian-Kui Shuai, Department of Critical Care Medicine, The Donggang District of First Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, China
Xi-Ping Sheng, Institute of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, Gansu Province, China
Yong-Xun Zhao, Department of Surgical Oncology, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Yu-Min Li, Key Laboratory of Digestive System Tumors of Gansu Province, The Second Clinical Medical School of Lanzhou University, Lanzhou 730000, Gansu Province, China
Author contributions: Liu LP and Li YM designed the experiments; Sheng XP and Li B contributed to the statistical analyses; Zhao YX performed the experiments; Liu LP prepared the manuscript; Shuai TK and Li B conducted data collection.
Supported by the Natural Science Foundation of Gansu Province, No. 1506RJZA255; the National Natural Science Foundation of China, No. 81572437; the Open Topics of the Key Laboratory of Biological Treatment and Regenerative Medicine in Gansu Province, No. zdsyskfkt-201702; and the Fund of Donggang Branch, The First Hospital of Lanzhou University, No. ldyydgyn-201705.
Institutional review board statement: The study was approved by the Ethics Review Board of the First Hospital of Lanzhou University.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yu-Min Li, MD, PhD, Chief Doctor, Professor, Key Laboratory of Digestive System Tumors of Gansu Province, The Second Clinical Medical School of Lanzhou University, No. 82, Cuiyingmen, Chengguan District, Lanzhou 730000, Gansu Province, China.
liym@lzu.edu.cn
Telephone: +86-931-8912127 Fax: +86-931-8912127
Received: August 11, 2018
Peer-review started: August 13, 2018
First decision: August 27, 2018
Revised: September 2, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 28, 2018
Processing time: 76 Days and 21.5 Hours
AIM
To detect the mechanisms of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC).
METHODS
Specimens from 99 patients with GC were collected. The correlation among H. pylori infection, heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression, which was determined by immunohistochemistry, and the clinical features of GC was analysed using SPSS 22.0. Overall survival (OS) and relapse-free survival (RFS) of GC patients were estimated by the Kaplan-Meier method. Independent and multiple factors of HPA and MAPK with prognosis were determined with COX proportional hazards models. HPA and MAPK expression in MKN-45 cells infected with H. pylori was analysed using Western blot.
RESULTS
H. pylori infection was observed in 70 of 99 patients with GC (70.7%), which was significantly higher than that in healthy controls. H. pylori infection was related to lymph metastasis and expression of HPA and MAPK (P < 0.05); HPA expression was relevant to MAPK expression (P = 0.024). HPA and MAPK expression in MKN-45 cells was significantly upregulated following H. pylori infection and peaked at 24 h and 60 min, before decreasing (P < 0.05). SB203580, an inhibitor of MAPK, significantly decreased HPA expression. HPA was related to lymph metastasis and invasive depth. HPA positive GC cases and H. pylori positive GC cases showed poorer prognosis than HPA negative cases (P < 0.05). COX models showed that the prognosis of GC was connected with HPA expression, lymph metastasis, tissue differentiation, and invasive depth.
CONCLUSION
H. pylori may promote the invasion and metastasis of GC by increasing HPA expression that may associate with MAPK activation, thus causing a poorer prognosis of GC.
Core tip: The mechanism of Helicobacter pylori (H. pylori) infection in the invasion and metastasis of gastric cancer (GC) is still unknown. This paper studied heparanase (HPA) and mitogen-activated protein kinase (MAPK) expression in GC tissues and GC cells and their relationship with H. pylori infection. H. pylori infection may promote the invasion and metastasis of GC by increasing the expression of HPA that may be increased by activation of MAPK signal and HPA expression in GC tissue. H. pylori positive GC had a poorer prognosis.
