| Objective: Gastric Cancer(GC)is a malignant tumor with high morbidity and mortality,and its pathogenesis is complicated.Although some progress has been made in the current diagnosis and treatment of gastric cancer,and a series of gastric cancer-related risk factors have been discovered,the overall prognosis of patients with gastric cancer remains unsatisfactory.Therefore,there is a critical need to find novel therapeutic targets to provide diagnosis and treatment options for more patients with gastric cancer,so as to improve the overall survival rate of patients with gastric cancer.Thrombospondins2(THBS2)is highly expressed in a variety of malignancies and is important for the development of lung adenocarcinoma,prostate cancer,myeloid neoplasms,and breast cancer as well as being closely associated with clinical prognosis.With the development of techniques in the field of bioinformatics,new advances have been made in the study of the pathogenesis,diagnosis,treatment and prevention of gastric cancer,which holds promise for further exploration of gastric cancer.In this study,a combined analysis of Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)databases revealed that THBS2 expression is associated with poor prognosis in patients with gastric cancer.Meanwhile,THBS2 may also affect Epithelial Mesenchymal Transition(EMT)in gastric cancer through PI3K/AKT signaling,further affecting gastric cancer migration and invasion.Therefore,we further investigated the relationship between the expression changes of THBS2 and the malignant biological behavior of gastric cancer and the underlying mechanism on the basis of pregerminal signal analysis.Methods: 1.The GEO database as well as the TCGA database were applied to screen Differentially Expressed Genes(DEGs)between cancer tissues and adjacent normal tissues from patients with gastric cancer.A prognostic risk model was established and evaluated utilizing Receiver Operating characteristic Curve(ROC)and Kaplan Meier survival curves.The correlation between the amount of THBS2 expression in gastric cancer expression datasets and clinicopathological factors in the TCGA database was further analyzed.2.To examine the expression of THBS2 in gastric cancer cells by Western blot,gastric cancer cells for subsequent analysis were selected.For THBS2 knock down experiments in selected gastric cancer cells,Western blot and q RT-PCR were used to determine the knock down efficiency.3.THBS2 was knocked down in selected gastric cancer cells,and the proliferation,migration,invasion,and apoptosis abilities of gastric cancer cells were detected by CCK-8,Transwell,and flow cytometry assays.4.The expression changes of EMT related proteins E-cadherin and N-cadherin and apoptosis related proteins Caspase-3 and Caspase-9 in gastric cancer cells after knock down of THBS2 were detected by Western blot.5.The effects of THBS2 knock down on the PI3K/AKT signaling pathway in gastric cancer cells were determined by Western blot.Results: 1.GEO and TCGA database analyses found that THBS2 expression was higher in gastric cancer tissues than in adjacent normal tissues,and was closely associated with poor prognosis in patients with gastric cancer.2.Western blot two kinds of gastric cancer cells,NCI-N87 and HGC-27,were selected as follow-up study cells;THBS2 was subjected to si RNA knock down experiments,and the No.3 si RNA with the highest knock down efficiency was selected for subsequent functional experiments.3.CCK-8assay,Transwell assay,flow cytometry results showed that knock down of THBS2 could inhibit gastric cancer cell proliferation,migration and invasion and promote gastric cancer cell apoptosis.4.Western blot verified that THBS2 could affect the biological progression of gastric cancer cells through the PI3K/AKT signaling pathway.Conclusions: 1.There is a correlation between THBS2 and poor prognosis in gastric cancer.2.The expression profile of THBS2 is associated with the malignant biological behavior of gastric cancer cells.3.THBS2 can regulate the EMT process in gastric cancer cells through the PI3K/AKT signaling pathway. |
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