Helicobacter pylori promotes invasion and metastasis of gastric cancer by enhancing heparanase expression  

作　　者：Li-Ping Liu Xi-Ping Sheng Tian-Kui Shuai Yong-Xun Zhao Bin Li Yu-Min Li 

机构地区：[1]The Second Clinical Medical School of Lanzhou University,Lanzhou 730000,Gansu Province,China [2]Department of Critical Care Medicine,The First Hospital of Lanzhou University,Lanzhou 730000,Gansu Province,China [3]Department of Critical Care Medicine,The Donggang District of First Hospital of Lanzhou University,Lanzhou 730030,Gansu Province,China [4]Institute of Epidemiology and Health Statistics,School of Public Health,Lanzhou University,Lanzhou 730000,Gansu Province,China [5]Department of Surgical Oncology,The First Hospital of Lanzhou University,Lanzhou 730000,Gansu Province,China [6]Key Laboratory of Digestive System Tumors of Gansu Province,The Second Clinical Medical School of Lanzhou University,Lanzhou 730000,Gansu Province,China

出　　处：《World Journal of Gastroenterology》2018年第40期4565-4577,共13页世界胃肠病学杂志（英文版）

基　　金：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;the Fund of Donggang Branch,The First Hospital of Lanzhou University,No.ldyydgyn-201705

摘　　要：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 KaplanMeier 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.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 KaplanMeier 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.

关 键 词：Gastric cancer HELICOBACTER PYLORI HEPARANASE MITOGEN-ACTIVATED protein kinase Overall SURVIVAL Relapse-free SURVIVAL 

分 类 号：R57[医药卫生—消化系统]