The Role Of P42.3 Target Gene ERM In Gastric Carcinoma And The Clinical Treatment Of Early Gastric Cancer

Bacground: Gastric adenocarcinoma is result from genes mutation accumulation by various factors.Most gastric adenocarcinoma is developed from the precancerous diseases(mainly chronic atrophic gastritis).Early diagnosis and treatment is the key point management of gastric adenocarcinoma.It's important to study the molecular mechanism of gastric adenocarcinoma for discovering diagnostic or therapeutic target for early intervention.Gastric cancer remains a therapeutic challenge with a 5-year survival of only20%~25%.Endoscopic submucosal dissection has become a standard treatment for early gastric cancer with a 5-year survival more than 90%.Therefore,it is important to have an accurate diagnosis of the cancer borders for obtaining a complete resection.This study aimed to systematically assess the relevant risk factors of positive lateral margin after en bloc resection of early gastric cancer.We hope this can be helpful for endoscopists.Part ? The expression and role of the p42.3 target gene ERM in gastric carcinoma tissue and cellinesAIMS:Gastric cancer is a multi-factor,multi-step pathological process,the innitiation step is known as chronic gastric mucosal inflammation.Our study demonstrated that Helicobacter pylori(H.pylori)could invoke p42.3 gene expression and it could be an early molecular event during the development from gastritis to gastric cancer,but the malignant transformation mechanism of the p42.3 remains unclear.In this study,we performed gene microarray after knock-down p42.3 in gastric cell line for figure out the downatream genes.We aimed at genes which is associated with cell proliferation,motility,migration and invasion.Methods: We first performed gene microarray after p42.3 knock-down to figure out the downstream genes.Then we testified the expression of ERM in 36 cancer tissues by mRNA.We detected the expression of p42.3 and ERM by immunohistochemical staining in 72 tissue specimens of normal gastric mucosal,chronic atrophic gastritis,intestinal metaplasia and gastric adenocaicinoma tissues,and analysised the relationship betweet ERM and p42.3gene.By RNA interference we detected the effects of knock-down ERM expression on apoptosis,proliferation and invasion.Results:1.We found that by high throughput microarray screening a considerable part of p42.3 downstream gene was ERM which was influenced by the p42.3 in the mRNA and protein level.2.The exprssion of ERM in cancer tissues was much higher than normal tissues in the mRNA level(p<0.026).3.In normal gastric mucosal,chronic atrophic gastritis,chronic atrophic gastritis with intestinal metaplasia and gastric adenocarcinoma tissue specimen,the expression level of p42.3 and ERM both were increasing gradually with the aggravation of pathological status(p<0.05).The expression level of ERM was positive related to the expression level of p42.3(r=0.742,p<0.05).Down-regulation of ERM resulted in increasing apoptosis,proliferation and invasion inhibited in gastric cancer cell line.Conclusion:Our study suggests that ERM was the target of p42.3 which affects the development and progressing of gastric cancer.It regulates the proliferation,invasion and metastasis of gastric cancer in cell line.Part ? Relevant risk factors for positive lateral margin after en bloc endoscopic submucosal dissection for early gastric adenocarcinomaAims: Endoscopic submucosal dissection is currently a standard treatment for early gastric cancer.It is important to have an accurate diagnosis of the cancer borders for obtaining a complete resection.This study aimed to systematically assess the relevant risk factors of positive lateral margin after en bloc resection of early gastric cancer.Methods: We retrospectively studied 355 Endoscopic submucosal dissection procedures for gastric epithelial neoplasms from 2009 to 2015.A total of 242 lesions were extracted and all were grouped by their lateral margin status.Clinicopathological features and risk factors for a positive lateral margin were analyzed.Results: The curative rate was 82.2% and the incidence of a positive lateral margin was12.4%.By univariate analysis,a positive lateral margin was found to be significantly associated with the tumor location,size,histological findings,lymphovascular invasion and invasion depth.Moreover,a positive lateral margin has a higher incidence of recurrent or residual tumors.A multivariate analysis showed that the location,diameter and histological classification of tumors were independent risk factors for positive resection margins.Conclusion: A positive lateral margin is closely related to the upper third of stomach,a tumor larger than 3cm and a mixed-type carcinoma.Additionally,the positive lateral margin has a predilection for recurrent or residual tumors.