Effect Of KDM6A Expression On Prognosis Of Gastric Cancer And Its Mechanism

Objective: KDM6 A participates in the development of tumors through the epigenetic mechanism of demethylation or acetylation of histone H3K27,and has been shown to participate in the development of various tumors.This study explored the relationship between KDM6 A mutations and expression and patient prognosis and clinical pathological factors,and further explored the molecular mechanism of KDM6 A involved in the development of gastric cancer.This study aims to discuss the effects of KDM6 A mutation and expression on the prognosis of patients,discuss its relationship with clinical pathological factors,and further explore the molecular mechanism of KDM6 A involved in the development of gastric cancer.Methods: 57 patients with gastric cancer were analyzed by full exon sequencing to analyze the relationship between mutations of KDM6 A and patient prognosis.Through correlation analysis in the Cbioportal,Kaplan Meier-Plotter and The Human Protein Atlas databases,got a preliminary understanding of the relationship among KDM6 A expression and clinicopathological factors of gastric cancer and the prognosis of patients.Gastric cancer tissue and the corresponding tissue adjacent to cancer tissue were collected from 107 gastric cancer patients,and the expression of KDM6 A was detected by immunohistochemistry,and the relationship between KDM6 A expression and clinical pathological factors was further analyzed;KDM6A knockdown model was established through cell culture and transfection technology to explore the molecular mechanism of KDM6 A in the occurrence and development of gastric cancer.Results: Analysis of the sequencing results of 57 patients with gastric cancer showed that patients with KDM6 A mutation had shorter survival time(P<0.05),and the mutations had statistical significance in clinicopathological factors such as Borrmann classification,T stage,TNM stage,and tumor diameter.Significance(P <0.05);In the bioinformatics database,it was found that patients with KDM6 A mutations and low expression had shorter overall survival and progression-free survival(P <0.05).The overall survival of patients with high KDM6 A expression was longer in stage III,intestinal,and diffuse patients,and the difference was statistically significant.The expression of KDM6 A protein in gastric cancer tissues is lower than that in normal gastric tissues.Wax tissues from 107 patients with gastric cancer were taken for immunohistochemical experiments and the results were analyzed.It is concluded that the expression of KDM6 A in paracancerous tissues is significantly higher than that in cancerous tissues,and the difference has statistical significant(P <0.001).In terms of clinical pathological factors,the expression of KDM6 A and the degree of differentiation of tumor tissues,T stage,N stage,and there was a correlation between TNM stages.Survival analysis showed that patients with high expression of KDM6 A had longer overall survival time(P <0.001);After establishing a cell model of KDM6 A knockdown,it was found that the tumor cell proliferation efficiency of KDM6 A knockdown was significantly higher than that of control cells(P <0.01),the expression of E-cadherin decreased significantly,and the expression of Vimentin and N-cadherin increased significantly in EMT.Conclusions: KDM6 A acts as a tumor suppressor gene in gastric cancer.Patients with KDM6 A mutations and low expression have shorter survival time.KDM6 A knockdown increases the proliferation capacity of tumor cells and induces EMT in gastric cancer cells.