| Background and purpose:Gastric cancer is a common malignant tumor of digestive tract in China.According to cancer statistics of China in 2015,the incidence and mortality rate of gastric cancer ranked second among all tumor types.Gastric cancer is highly heterogeneous,insidious and progresses rapidly with a 5-year survival rate of less than 30%.Radical resection is the most effective treatment for gastric cancer.However,more than 80% of patients are in advanced stage when they seek medical treatment and lose the opportunity of surgery.In recent years,with the development and application of chemical drugs,more attention has been paid to the clinical efficacy of surgery combined with chemotherapy.The study indicates that pre-operative Neoadjuvant chemotherapy(NAC)can reduce the tumor stage,enhance the R0 resection rate and prolong the total survival time compared with the single operation.PI3K-AKT-mTOR signaling pathway is also called phosphoinositide-3 kinase-protein kinase B-mechanistic target of rapamycin kinase signaling pathway,it is a classical anti-apoptosis and pro-survival signal transduction pathway,playing a key regulatory role in cell growth,proliferation,survival,migration and other aspects.Under the stimulation of various cytokines,the PI3K-AKT-mTOR signaling pathway is abnormally over-activated,increasing the cascade amplification of downstream signals,which plays a central role in the malignant progression of gastric cancer.MTOR signaling molecules are central to regulating growth,and abnormal activity of mTOR can induce malignant tumor formation.Studies have found that mTOR can also be used to evaluate the biological characteristics and prognosis of gastric cancer,and it is also one of the targets of tumor treatment.E-cadherin is a family member of cell adhesion molecules,which is most closely related to tumor metastasis.Octamer binding transcription factor 4 over expression can also lead to the formation of different types of tumor and metastasis.Most previous studies focused on the expression of individual signaling molecules in the PI3K-AKT-mTOR signaling pathway in gastric cancer tissues.However,the correlation between activation,feedback form,up-regulation and down-regulation of the signaling pathway and clinical characteristics remains to be clarified.Although studies on the expression of e-cadherin and OCT4 proteins are common in gastric cancer,there are few studies on the expression of neoadjuvant chemotherapy.Gastric cancer patients have poor prognosis,low 5-year survival rate,and lack of protein signals to effectively evaluate prognosis.In this study,changes in PI3K-AKT-mTOR signaling pathway protein,E-cadherin and OCT4 protein expression in tissue samples of gastric cancer patients before and after neoadjuvant chemotherapy are used to evaluate the objective response rate of chemotherapy drug,which further explore the relationship between the expression of PI3K-AKT-mTOR signaling pathway protein,E-cadherin and OCT4 protein in gastric cancer tissues before and after neoadjuvant chemotherapy and the clinical phenotype and prognosis of gastric cancer patients.Method:Retrospectively collected the Affiliated Cancer Hospital of Zhengzhou University,from January 2012 to December 2016,menstrual gastroscopy pathological diagnosis of gastric cancer,and received neoadjuvant chemotherapy regimens(oxaliplatin+ fluorouracil into class for Tegafur,Gimeracil and Oteracil Potassium Capsules/capecitabine),greater than or equal to 2 cycles,neoadjuvant chemotherapy(gastroscope pathological specimens)before and after neoadjuvant chemotherapy(accept gastric cancer after radical resection of gastric cancer tissue samples)pathological and clinical data of cases of complete,and forty cases of eligible patients were screened.Immunohistochemistry(SP method,namely streptomycetin protein-peroxidase binding method)was used to detect the expression of PI3K-AKT-mTOR signaling pathway protein,E-cadherin and OCT4 protein in gastric cancer tissue samples before and after neoadjuvant chemotherapy,and the relationship between protein expression level before and after neoadjuvant chemotherapy and survival and prognosis was analyzed.Results:1.Among the 40 patients,30(30/40,75%)were male and 10(10/40,25%)were female.The median age was 59(45 to 75 years old).With neoadjuvant chemotherapy,the PR rate was 60%(24/40).Twenty-six patients(26/40,65%)showed tumor regression of TRG 3,but no complete regression of TRG4.2.Univariate analysis: the expressions of PI3K-AKT-mTOR,E-cadherin and OCT4 before and after NAC were correlated with the differentiation degree of gastric cancer tissues,and the differences were statistically significant(P<0.05).However,the expression of mTOR protein before and after NAC was correlated with lymph node metastasis(P<0.05),gender,age,tumor size,tumor site,invasion depth,presence or absence of lymph node metastasis,and grade of tumor regression were not correlated with protein expression.3.The expressions of p-AKT protein before NAC and p85,mTOR,E-cadherin and OCT4 protein after NAC were correlated with DFS.However,the DFS of the E-cadherin positive group was longer than that of the negative group,the DFS of the other protein negative group were all better than that of the positive group(p <0.05).4.P-AKT and mTOR proteins before and after NAC,and p85,E-cadherin,OCT4 protein expressions after NAC were correlated with mOS.However,the mOS of the E-cadherin positive group was longer than that of the negative group,and mOS of the other protein negative groups were higher than that of the positive group,and the difference was statistically significant(p <0.05).5.Negative and positive proteins before and after NAC were grouped into COX regression model,and it was found that changes in protein indexes before NAC did not affect DFS,while mTOR,E-cadherin and OCT4 proteins after NAC were important risk factors affecting DFS.MTOR protein before and after NAC,and p85,p-AKT protein changes after NAC were risk factors affecting mOS(p <0.05).6.Negative and positive proteins before and after NAC were grouped entry into Kaplan-Meier subsistence analysis,and it was found that the DFS and mOS of the negative-negative group before and after neoadjuvant chemotherapy(p85,p-AKT,mTOR)were higher than those of the positive-positive group,negative-positive group and positive-negative group.The DFS and mOS of E-cadherin protein in the negative-positive group before and after NAC were better than those in the other groups.The DFS and mOS of OCT4 protein in the positive-negative group before and after NAC were better than those in the other groups(P<0.05).7.Protein indexes of each variable were combined and input into COX regression model one by one,and no risk factors affecting DFS were found,while p-AKT protein index changes before and after NAC were independent risk factors affecting mOS(p =0.036).Conclusion:1.After neoadjuvant chemotherapy,the expression of p85,p-AKT,mTOR and OCT4 was negative,while the expression of E-cadherin was positive,which was an indicator to reduce the recurrence of gastric cancer and prolong survival.2.Before and after neoadjuvant chemotherapy,DFS and mOS of p85,p-AKT,mTOR negative-negative group,E-cadherin negative-positive group and OCT4 negative-positive group were longer and had better prognosis. |
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