| Background: Gastric cancer is one of the most common gastrointestinal malignancies in the world.It has a poor prognosis and seriously threatens human health.Its occurrence and development are a long-term process with multiple factors interacting with each other,involving activation of oncogenes,inactivation of tumor suppressor genes,abnormalities in intracellular signaling pathways,and the combined action of multiple biological factors.According to the latest statistics from GLOBOCAN,in 2018,there were approximately 1.033 million new cases of gastric cancer(1/18)and approximately783,000 cases(1/12)of deaths,respectively,ranking 5th in morbidity and 2nd in mortality.In China,the incidence of gastric cancer is ranked second in malignant tumors,and the mortality rate is ranked third.In recent years,it has continued to rise and become younger.Gastric cancer often has no obvious conscious symptoms in the early stage,and it is often in the middle and advanced stages when it is discovered,which leads to poor treatment effect,poor quality of life,and poor prognosis.In addition to improving the original traditional treatment measures,in recent years,targeted therapy has become the focus of international research.Finding suitable tumor treatment targets has become a hope for curing malignant tumors.Hepatocyte growth factor and its receptor(HGF/c-Met)signaling pathway is closely related to the occurrence,development,metastasis and prognosis of gastric cancer,and ERK pathway is an important part of it,and it is also a very targeted therapy for gastric cancer.Potential pathways will help the diagnosis and treatment of gastric cancer.The purpose of this study was to use clinical epidemiological data such as clinical,pathological,and follow-up information of gastric cancer patients accumulated in the database of the Ministry of Education’s Key Laboratory Database of Gastrointestinal Tumor Surgery and the Ministry of Education’s Key Laboratory of Gastrointestinal Tumor Surgery.Using immunohistochemical techniques to analyze the effects of HGF on clinicopathological characteristics and prognosis of gastric cancer;the cell biology part,using cell biology methods to discover the impact on the cell proliferation and migration.Provide theoretical basis for screening,early diagnosis and targeted treatment of high-risk populations of gastric cancer in China.Part Ⅰ Expression of HGF,c-Met and p-Erk molecules in gastric cancer and the survival analysisObjective: This study investigated the relationship of hepatocyte growth factor(HGF),mesenchymal epithelial transition factor(c-Met),phosphorylated Erk(p-Erk)expression and clinicopathology characteristics of gastric cancer.To investigate whether HGF,c-Met,and p-Erk expressions have a significant effect on the survival of patients with gastric cancer.Methods: The expressions of HGF,c-Met and p-Erk in 71 cases of gastric cancer and 53 cases of adjacent normal tissues were detected by immunohistochemistry.The relationship between HGF,c-Met and p-Erk was analyzed.The correlation between the expression in gastric cancer tissues and clinicopathology characteristics was also analyzed,and then the survival rate of five years was calculated.Survival K-M curve and COX multiple factors analysis,and through the analysis of KM-plotter,the prognosis of patients with gastric cancer data in the database to explore the HGF,c-Met,p-Erk expression of survival in patients with gastric cancer were performed.Results: The expression of HGF,c-Met and p-Erk in gastric cancer tissues was significantly higher than that in adjacent normal tissues(P < 0.05).The expressions of them in gastric cancer tissues were not related to gender,age,main cancer location,pathological tissue classification(P > 0.05),but were significantly related with the main cancer size,pathological tissue growth pattern,depth of invasion,lymph node metastasis,and recurrence or metastasis(P < 0.05).In gastric cancer tissues,p-Erk was positively correlated with HGF expression(r = 0.666,P < 0.05),and p-Erk was positively correlated with c-Met expression(r = 0.587,P < 0.05).The expression of C-Met was positively correlated with HGF expression(r = 0.576,P < 0.05).The expression of HGF,c-Met and p-Erk were significantly had lower survival rate of five years.KM-plotter database showed that the expression of HGF、c-met and p-Erk in gastric cancer tissue increased poor prognosis.Applying Cox proportional hazards model analysis,single factor analysis showed that the main size,infiltrating depth,with or without lymph node metastasis and recurrence occurred and degree of the expression of them in gastric cancer can significantly affect the prognosis of patients with gastric cancer.Results show that the recurrence and p-Erk expression level were independent prognostic factors for patients with gastric cancer.Conclusion: The expression of HGF,c-Met and p-Erk were significantly increased in gastric cancer tissues.Thy were closely related to the occurrence and development of gastric cancer,and might participate in the process of gastric cancer.Part Ⅱ The effect of HGF/c-Met and downstream Erk signaling pathway on the cell proliferation and migration ability of gastric cancer cell MGC803Objective: To study the effects of HGF/c-Met and downstream Erk signaling pathway on the proliferation and migration of gastric cancer cell line MGC803,and to explore the role and possible mechanism of this signaling pathway in promoting gastric cancer cell proliferation and migration.Methods: Gastric cancer cells MGC803 were cultured in vitro and divided into different groups MGC803,MGC803+1ng/ml HGF,MGC803+100ng/ml HGF,MGC803+100ng/ml HGF+Crizotinib(c-met inhibitor),MGC803+100ng/ml HGF+U0126(erk inhibitor),cell scratch test and MTT test to detect cell proliferation and observe cell migration.Results: HGF up-regulated the gastric cancer MGC803 proliferation and its migration in a concentration-and time-dependent manner.C-met inhibitors and erk inhibitors significantly downregulated these effects on MGC803.Conclusion: HGF/c-Met and downstream Erk signaling pathway can significantly increase the proliferation and migration of gastric cancer cell MGC803.When HGF/c-Met and downstream Erk signaling pathway were inhibited,the proliferation and migration of gastric cancer cell MGC803 were significantly suppressed. |
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