Interaction Between Key Protein Expression Of PI3K/Akt/mTOR Signaling Pathway And Environmental Risk Factors In Gastric Cancer

Objectives:1.To analyze the differential expression of key proteins such as PI3K,mTOR,and PTEN in poorly differentiated gastric cancer cell line BGC-823,moderately differentiated gastric cancer cell line SGC-7901 and normal gastric mucosal epithelial GES-1 and to test the Activation of PI3K/Akt/mTOR signaling pathway in gastric cancer.2.To analyze the differential expression of PI3K,PTEN,mTOR and other key proteins in PI3K/Akt/mTOR signaling pathway in gastric cancer patients and healthy people,and to explore the activation of PI3K/Akt/mTOR signaling pathway in peripheral blood mononuclear cells.To explore the correlation between PI3K,PTEN,mTOR and its phosphorylated forms p-PI3K,p-mTOR,p-PTEN and gastric carcinogenesis.3.To screen the environmental risk factors of gastric cancer,and study the interaction between pathogenic factors and environmental risk factors in the development of gastric cancer.Method:1.Cultured human poorly differentiated gastric cancer cell line SGC-7901,moderately differentiated gastric cancer cell line BGC-823 and normal gastric mucosal epithelial cell GES-1 in vitro,and detected quantitative expression of total protein PI3K?mTOR?PTEN?p-PI3K?p-mTOR and p-PTEN by Western Blot.2.74 patients with newly diagnosed gastric cancer and 70 healthy people were randomly selected.Peripheral blood mononuclear cells were extracted from both groups.Western blot was used to detect Quantitative expression of total protein PI3K,mTOR,PTEN and phosphorylated protein p-PI3K,p-mTOR,p-PTEN in peripheral blood mononuclear cells.3.Gastric cancer patients and healthy people were investigated using the same method using a unified questionnaire.Including general conditions such as age,gender,family history of diseases and cancer,diet,smoking and drinking habits.According to the second chapter Western Blot method,the expression of key proteins in PI3K/Akt/mTOR signaling pathway was detected by logistic regression.Logistic regression was used to analyze the interaction between environmental risk factors and protein expression in gastric carcinogenesis.Result:1.Expression of key signal molecules of PI3K/Akt/mTOR signaling pathway in SGC-7901,BGC-823 and GES-1 cellsWestern Blot results showed that the protein expression of PI3K?p-PI3K?mTOR and p-mTOR in gastric cancer cells SGC-7901 and BGC-823 was significantly higher than that in normal gastric mucosal epithelial cells?P<0.05?.The expression of PTEN and p-PTEN protein in normal gastric mucosal epithelial cells GES-1 was significantly higher than that in common gastric cancer cells SGC-7901and BGC-823?P<0.05?.2.Expression of key signal molecules of PI3K/Akt/mTOR signaling pathway in peripheral blood mononuclear cells of gastric cancer population and healthy populationThe protein expression levels of PI3K,p-PI3k and p-mTOR in the case group were significantly higher than those in the control group,and the difference was statistically significant?P<0.05?.There was no significant difference in total protein mTOR expression between the two groups?P>0.05?.The protein expression of PTEN in the case group was significantly lower than that in the control group.?P<0.01?.The expression of p-PTEN in the case group was not significantly different from that in the control group?P>0.05?.Multivariate logistic regression analysis was performed on key proteins such as PI3K,p-PI3K,p-mTOR,and PTEN based on single factor analysis.After correction by gender and other factors,the expression of p-PI3K was significantly correlated with the occurrence of gastric cancer?OR=1.501;95%CI=1.085-2.074;P<0.05?.The expression of p-mTOR was significantly associated with the risk of gastric cancer.High expression of p-mTOR may increase the risk of gastric cancer?OR=1.462;95%CI=1.055-2.027;P<0.05?.The expression of PI3K was not associated with the occurrence of gastric cancer?OR=1.095;95%CI=0.768-1.562;P>0.05?,and there was no significant correlation between the expression of PTEN and gastric cancer?OR=0.730;95%CI=0.527-1.012;P>0.05?.3.The interaction between key protein expression of 3.PI3K/Akt/mTOR signaling pathway and environmental risk factors in gastric cancer3.1 The chi-square test showed that there was no significant difference in the distribution of age,gender,drinking,tea drinking,and spicy food between the case group and the control group?P>0.05?.The high school students in the case group were significantly lower than the control group?P<0.05?.There were more cases of family history of digestive diseases in the case group than in the control group,and the difference was statistically significant?P<0.05?.The family history of tumors in the case group was significantly higher than that in the control group,and the difference was statistically significant?P<0.05?.The number of smokers in the case group was significantly higher than that in the control group,and the difference was statistically significant?P<0.05?.The fresh vegetables in the case group were significantly less than the control group,and the difference was statistically significant?P<0.05?.The number of people who like to eat preserved food in the case group was significantly higher than that in the control group,and the difference was statistically significant?P<0.05?.In the case group,those who like fried foods were significantly different from the control group?P<0.01?.Logistic regression results showed that the risk of gastric cancer in patients with a family history of digestive diseases was 2.516 times?95%CI=1.139-5.558;P<0.05?.Patients with a family history of cancer had a significantly increased risk of developing gastric cancer compared with non-tumor family history?OR=3.449;95%CI=1.220-9.699;P<0.05?.The risk of stomach cancer in smokers was 2.815 times that of non-smokers?95%CI=1.287-6.155;P<0.05?.The risk of stomach cancer was 2.510times higher than that of fresh vegetables?95%CI=1.077-5.847;P<0.05?,eating fresh vegetables is a protective factor for gastric cancer.Eating fried foods significantly increased the risk of gastric cancer?OR=2.858;95%CI=1.155-7.068;P<0.05?.There was no significant correlation between the eaten food and the incidence of gastric cancer?OR=1.793;95%CI=0.597-5.387;P>0.05?.3.2 Logistic regression analysis of the interaction of PI3K,p-PI3K,PTEN,p-mTOR with environmental risk factors.There was an interaction between p-PI3K and those family history of digestive diseases,?OR=1.710;95%CI=1.179-2.480;P<0.05?.With a family history of digestive diseases,with a gradient of p-PI3K expression,the risk of gastric cancer increases by 211.6%(OR_eg=e^?e+?g=3.116).p-PI3K interacted with those who liked fried foods?OR=0.459;95%CI=0.237-0.891;P<0.05?.For those who like fried foods,the risk of gastric cancer decreases by 16.4%(OR_eg=e^?e+?g=0.836)with a gradient of p-PI3K expression.PTEN interacts with those who like fried foods?OR=3.153;95%CI=1.603-6.204;P<0.01?,and the risk of gastric cancer decreases with each additional gradient of PTEN protein expression in those who eat fried foods.11.4%(OR_eg=e^?e+?g=0.886).PTEN expression interacted with tea drinking?OR=2.367;95%CI=1.023-5.474;P<0.05?,and the risk of gastric cancer decreased by 33.5%with increasing gradient of PTEN expression in non-tea drinking patients.OR_eg=e^?e+?g=0.665).Among those with high PTEN expression,the risk of gastric cancer was lower by 88.4%(OR_eg=e^?e+?g=0.116).There was an interaction between PTEN expression and family history of tumors?OR=1.914;95%CI=1.253-2.924;P<0.01?.With a family history of tumors,the risk of gastric cancer decreased by 46.2%with each additional gradient of PTEN expression(OR_eg=e^?e+?g=0.538).At the same time,the results showed that mTOR expression and smoking had an interaction?OR=1.919;95%CI=1.292-2.852;P<0.01?.Conclusions1.The PI3K/Akt/mTOR signaling pathway is activated in the gastric cancer cell.The abnormal activation of this signaling pathway is closely related to the occurrence and development of tumor.2.PI3K/Akt/mTOR signaling pathway is activated in mononuclear cells of gastric cancer population,partial oncogene activation,inactivation of tumor suppressor gene,leading to poor progression of gastric cancer,and the expression of key proteins in this signaling pathway increases gastric cancer.The risk of development reveals a poor progression of the PI3K/Akt/mTOR signaling pathway in the population.3.Smoking,poor eating habits,and family history of cancer are risk factors for gastric cancer,and eating fresh vegetables is a protective factor for gastric cancer.The interaction of some environmental factors with the expression of key proteins in the PI3K/Akt/mTOR signaling pathway is particularly important in the pathogenesis of gastric cancer,suggesting that people should explore the development of gastric cancer from both genetic and environmental aspects and seek prevention and treatment of gastric cancer.