Study On The Relationship Between MTOR And MAP1LC3B And The Development Of Breast Cancer

Cancer has become the second largest threat to human health,become a worldwide public health problems.In women,breast cancer has risen to the first incidence of mortality,the second death rate of cancer.More and more research has focused on the relationship between the immune system disorders and cancers.Autophagy is an important part of the immune system,in recent years,more and more evidence shows that autophagy and breast cancer development process have a very close relationship.The autophagy process is mainly regulated by the mTOR signaling pathway and the PIK3 signaling pathway.Under physiological conditions,the mTOR pathway inhibits autophagy.In the case of starvation,malnutrition,or in vivo,the activity of mTOR is inhibited and ULK is activated to induce the initiation of cell autophagy.Thus,the mTOR signaling pathway acts as a role of inducing autophagy initiation.MAP1LC3 B is located on the mature autophagic membrane,which represents the formation and maturation of autophagosomes,so its number is positively related to the number of autophagosomes.In this study,we used TCGA data,pathological analysis and cell culture experiments to study the relationship between mTOR and MAP1LC3 B and the development and progress of breast cancers in order to provide the basic data for the treatment of breast cancers.First,the gene expression data and clinical data of 1067 patients with breast cancer were obtained from the TCGA database(The Cancer Genome Atlas)to analyze the expression patterns of autophagy-related genes in tumor tissues and adjacent tissues,different tumor grades and different tumor stages.Then we did related cytology and clinical histology experiments to verify the accuracy of these differences in expression.At the same time,we divided the patients into high(50%)and low(50%)groups according to the expression of autophagy-related genes(MAP1LC3B and mTOR)and analyzed the overall survival analysis to observe the effect of expression of autophagy-related genes on the survival rate of cancer patients.Using the TCGA database,it was found that the expression of autophagy-related genes in breast cancer were lower than that in normal breast tissues,and there was no significant difference between MAP1LC3 A,BECN1 and Rab7 a in breast cancers and normal breast tissue.And then we analyzed the core genes mTOR and MAP1LC3 B in autophgy process for further in-depth analysis and experiments.The expression of mTOR and MAP1LC3 B genes in four breast cancer types was similar.The expression of mTOR and MAP1LC3 B genes in different types of breast cancer was significantly different.High expression of mTOR and MAP1LC3 B in basal-like and HER-2 breast cancers with a high degree of malignancy and a lower expression in Luminal A / B breast cancer with a lower degree of malignancy.Breast cancer TNM stages I,Ⅱ stages for the early,Ⅲ,Ⅳ stages for the late,late stages relative to the early have higher degree of malignancy,poorer prognosis,lower survival rate.By analyzing the expression of two genes differences in the TCGA database,it was found that the autophagy-related genes m TOR and MAP1LC3 B were higher in stage Ⅲ and Ⅳ than in stage I and Ⅱ.On the basis of the above points,the effects of mTOR and MAP1LC3 B genes expression on the survival rate of patients were further analyzed.Two genes were divided patients into high and low groups(50%)for survival analysis based on the level of expression,we found that the expression level of MAP1LC3 B and mTOR had a significant effect on the survival time of patients.The higher survival rate of patients had lower expression of autophagy-related genes MAP1LC3 B and mTOR,the lower the survival rate of patients had higher genes expression.This result has a certain correlation with the differences in the expression levels of the two genes analyzed in different types and stages.The expression differences of autophagy-related genes mTOR and MAP1LC3 B in breast cancers and normal breast tissues were analyzed by histopathological analysis.The results of histological experiments and database analysis were consistent.The two genes showed that the expression of m TOR and MAP1LC3 B in the tumorswas lower than normal Breast tissues.The expression of mTOR and MAP1LC3 B in the different types of breast cancers were detected by immunohistochemical staining and western blotting in Pathology tissues and cultured breast cancer cells.The lower expression in lower level of malignancy.In this study,we analyzed the relationship between the expression of mTOR and MAP1LC3 B and the degree of malignancy.It was found that there were different expression patterns in tumor tissue,different PAM50 types and different clinical grade samples.And this up-regulation or down-regulation has a different but important impact on the development and prognosis of breast cancers.This study provides a theoretical basis for the future treatment of breast cancer through the regulation of autophagy-related gene expression.