Analysis Of The Correlation Between ADAMTS18 And The Prognosis Of Gastriccancer And Its Effect On The Biological Function

Research content: This study was divided into three chapters: 1.The relationship between metalloproteinase ADAMTS18 and the clinical prognosis of gastric cancer;2.The relationship between ADAMTS18 gene and clinicopathological features of gastric cancer;3.The effect of ADAMTS18 gene silencing and overexpression on the biological behavior of gastric cancer cells.Chapter one the relationship between metalloproteinase adamts18 and the clinical prognosis of gastric cancer based on tcga databaseObjective:To investigate the expression and clinical value of metalloproteinase ADAMTS18 in gastric cancer,and to predict the possible mechanism of ADAMTS18 to regulate tumor development.Methods:The differences in Expression levels of ADAMTS18 in gastric cancer tissues and normal gastric tissues were analyzed online from the Analysis tool,Gene Expression Profiling Interactive Analysis.The datasets of gastric cancer were collected from The Cancer Genome Atlas(TCGA).Relationship between ADAMTS18 expression and clinicopathologicalparameters were analyzed and prognostic survival analysis of ADAMTS18 in TCGA were analyzed with Kaplan–Meier survival analysis and the log-rank test and multivariate survival analyses.Gene MANIA and STRING were used to constructed gene-gene interaction networks and protein-protein networks and Enrichment analysis of genes and signal paths of ADAMTS18 in tumor occurrence and development.Results:In the TCGA,the expression of ADAMTS18 was correlated with tumor grade(P<0.001).High expression of ADAMTS18 indicated poor prognosis(P=0.002 HR=1.809,95%CI=1.236-2.649).Enrichment analysis of ADAMTS18 was associated with extracellular matrix remodeling,tumor necrosis factor response and metal peptidase activity and others.Conclusion:ADAMTS18 is an adverse prognostic factor for gastric cancer and can be used as a potential prognostic marker.Chapter two the relationship between adamts18 gene and clinicopathological features of gastric cancerObjective: To investigate the expression of ADAMTS18 in gastric cancer tissue and to analyze its correlation with clinical pathological parameters.Methods: We collected 40 pairs gastric tissue and tissue adjacent to carcinoma as well as clinical pathological datas,diagnosed by Gastrointestinal surgery and pathology,in the First Affiliated Hospital of Guangxi Medical University from October 2016 to February 2017.Trizol was used to abstract total RNA from gastric tissue and tissue adjacent to carcinoma.QT-PCR was applied to measured ADAMTS18 m RNA expression levels.Furthermore,the correlation between ADAMTS18 m RNA and clinical pathological parameters was analyzed.Results: ADAMTS18 mRNA level was higher in gastric carcinoma tissue than adjacent tissue(P=0.001).ADAMTS18 protein levels was also higher in in gastric tumor tissue than adjacent tissue demonstrated by immunohistochemistry(P<0.001).ADAMTS18 m RNA levels was positively related with tumor differentiation,lymph node metastasis and TNM stage(P=0.013,P=0.001,P=0.001).Conclusion: ADAMTS18 is upregulated in gastric tumor tissue and it is positively related with tumor differentiation,lymph node metastasis and TNM stage.Chapter three the effect of adamts18 gene silencing and overexpression on the biological behavior of gastric cancer cellsObjective: To explore the effect of ADAMTS18 on malignant proliferation,migration and invasion abilities in Gastric cancer cell lines SGC-7901 and MGC-803.Methods: ADAMTS18 silence and overexpression stable cell line were constructed using lentivirus in SGC-7901 and MGC-803 cell lines.The efficiency of overexpression and silence of ADAMTS18 was measured by Qrt-PCR and Western Blot.MTT method was used to detect changes of proliferation.Wound healing assay and Transwell chamber were used to detect the ability to migrate in gastric cancer cell line after ADAMTS18 ovexpression and silence.Results: Silence and overexpression of ADAMTS18 were succeeding in constructed in gastric cancer cell line S SGC-7901 and MGC-803.Down-regulated of ADAMTS18 inhibited gastric cell line SGC-7901 and MGC-803 proliferation,migration and invasion abilities demonstrated with MTT method,wound healing assay and transwell chamber.Overexpression of ADAMTS18 enhanced gastric cell lines SGC-7901 and MGC-803 proliferation,migration and invasion abilities.Conclusion: Silence of ADAMTS18 by lentivirus suppress proliferation,migration and invasion abilities of gastric cancer cell lines.Overexpression of ADAMTS18 by lentivirus facilitate proliferation,migration and invasion abilities of gastric cancer cell line.