| Objectives:To identify genes correlated intimately with the occurrence and development of gastric cancer via bioinformatics analysis,and to explore the relationship between key genes and Helicobacter pylori infection preliminarily.Methods:Part Ⅰ:With gastric cancer-related dataset download in Gene Expression Omnibus,R software was applied to mine upregulated differentially expressed genes of gastric cancer.Furthermore,gene ontology functional enrichment analysis,Kyoto encyclopedia of genes and genomes pathway enrichment analysis and survival analysis on differential genes were performed combined with bioinformatics analysis to screen key genes associated with the occurrence and development of gastric cancer.Further analysis of the expression of key genes was conducted by immunohistochemistry in the collected gastric cancer tissues and corresponding paracancerous tissues.Part Ⅱ:Clinical data of enrolled subjects was collected,including blood samples,the Helicobacter pylori infection status,Body Mass Index(BMI),low-density lipoprotein(LDL)and apolipoprotein B(APOB),etc.The serum level of SERPINE1 was measured through enzyme-linked immunosorbent assay.The correlation between serum level of SERPINE1 and clinical data was evaluated by Spearman correlation analysis and chi-square test for trend.Meanwhile,Logistic regression analysis was conducted to evaluate the relationship between clinical data and Helicobacter pylori infection.In addition,the receiver operating characteristic curve was used to analyze the diagnostic value of the serum level of SERPINE1 for Helicobacter pylori infection.Results:Part I:SERPINE1 gene was highly expressed in gastric cancer tissues via the bioinformatics analysis,which was closely related to the poor prognosis of gastric cancer.Immunohistochemical test result confirmed that the protein expression of SERPINE1 was higher in gastric cancer tissues than that in paracancerous tissues(χ2=43.05,P<0.005).Part Ⅱ:The serum level of SERPINE1 protein in Helicobacter pylori-positive group was higher than that in Helicobacter pylori-negative group(P<0.001).Furthermore,the serum level of SERPINE1 protein showed a strong correlation with the status of Helicobacter pylori infection and the levels of BMI,LDL and APOB(P<0.001);subjects with higher levels of serum SERPINE1 protein had higher rates of Helicobacter pylori infection(P<0.001).Logistic regression analysis showed that BMI,SERPINE1,LDL and APOB were significantly correlated with Helicobacter pylori infection(P<0.001).In addition,the area under the receiver operating characteristic curve of the serum level of SERPINE1 protein was 0.906 in the diagnosis of Helicobacter pylori infection,and the predicted optimal cut-point value was 6.49 ng/ml,with the sensitivity value of 84.4%,the specificity value of 83.3%,and the Youden index of 0.677.Conclusion:Part Ⅰ:SERPINE1 gene is initially confirmed as a potential biomarker for the diagnosis,treatment,and prognosis evaluation of gastric cancer.Part Ⅱ:Helicobacter pylori may promote the progression of gastric cancer by activating a SERPINE1-mediated carcinogenic pathway.High serum level of SERPINE1 protein is expected to be one of the indications for Helicobacter pylori eradication.Helicobacter pylori infection may lead to lipid metabolism disorders,and SERPINE1 protein may participate in the regulation of lipid metabolism. |
