| Objective:Gastric cancer(GC)is one of the malignant tumors with high morbidity and mortality in the world,seriously threatened the life and health of people all over the world.Currently,the treatment of GC patients is still frustrating,early and middle stage gastric cancer mainly consists of surgery,adjuvant chemotherapy and radiotherapy.Although radical surgery combined with postoperative adjuvant therapy can further prolong the survival of tumor recurrence and metastasis in GC patients,the prognosis of gastric cancer is still not satisfactory.Recently,different genes have been found to play an important role in gastric cancer,but they still cannot explain the occurrence and development of all gastric cancers,suggesting that there are other molecular mechanisms in the development of gastric cancer that have not yet been revealed.Therefore,it is particularly urgent to explore the complex GC molecular mechanism,to find efficient molecular markers for the diagnosis and prognosis evaluation of GC patients and to find targeted therapeutic sites.The purpose of this study is to explore and validate potential markers of gastric cancer using bioinformatics methods.Methods:In the first part,downloaded the GSE84437 chip data in the GEO database and screened the differentially expressed target genes by using the gene expression analysis tool(GEO2R)and R software.After conducted survival analysis and independent prognostic analysis,the DEGs which is most related to the overall survival of gastric cancer patients,is selected as the target gene(ARHGAP 23).Volcano map,correlation analysis and heat map analysis are performed for the differentially expressed target genes(ARHGAP 23).GO enrichment analysis and KEGG pathway analysis are performed through DAVID database.The protein interaction network(PPI)of differential genes analyzed by STRING online software.In the second part,the expression of ARHGAP 23 in 180 patients who operated radical surgery for gastric cancer is observed by immunohistochemical method,then analyze its correlation with clinicopathologic features and prognostic information of GC patients.Results:A total of 787 differential genes are screened in GEO database.40 eligible target genes are obtained through three-step screening(clinicopathological feature filtering 、 k-m survival filtering and independent prognostic survival filtering).Based on the purpose of our study,we select ARHGAP 23 as the target gene.The target gene ARHGAP 23 is found to be highly expressed in T4 and N2 by clinicopathological analysis(P <0.001);The survival curve show that the five-year survival rate of the high expression group is lower than the low expression group(P <0.001);ARHGAP 23 is an independent prognostic factor for gastric cancer(P<0.001)in independent prognostic analysis.The correlation analysis between ARHGAP 23 gene and 60 DEGs which most significantly up-regulated and down-regulated showed that DPYSL3 is the gene with the strongest positive correlation.PPI is a protein interaction between ARHGAP 23 and the 60 DEGs most significantly up-regulated and down-regulated.In the functional enrichment analysis,ARHGAP 23 gene is involved in the negative regulation of typical Wnt signaling pathway,regulation of typical Wnt signaling pathway,tyrosine metabolism,phenylalanine metabolism,and chemical carcinogenic action pathway.Immunohistochemical results showed that the expression of ARHGAP 23 in gastric cancer tissues is significantly higher than that matched para-cancer tissues.In clinical characteristics,there are obvious differences in expression in different T grade,N grade and TNM stage,and the differences have statistically significant(P < 0.05).Meanwhile,the expression of ARHGAP 23 is confirmed as an independent factor affecting the prognosis of patients with gastric cancer by COX analysis(P < 0.05),which is consistent with the results of the GEO database.Conclusions:ARHGAP 23 is an independent prognostic factor for gastric cancer in GEO database.ARHGAP23 is highly expressed in gastric cancer tissues,which is associated with poor prognosis in GC patients,and it is verified that ARHGAP23 is also an independent prognostic factor in gastric cancer tissues,which is expected to be a new biomaker for future treatment of gastric cancer. |
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