| Background and objective: Gastric cancer is one of the most common malignant tumors in the digestive system worldwide.The incidence rate and mortality rate of gastric cancer are continuing high in the world.The incidence rate of gastric cancer is high in China and according to the statistics of cancer in 2015,the incidence rate and mortality rate of gastric cancer ranked the second in all malignant tumors.Due to the large population base,the incidence and mortality of gastric cancer in China account for about 50% of the total deaths of gastric cancer in the world.At present,there is still a lack of early diagnostic markers for gastric cancer.Most patients are diagnosed by endoscopy only when they present with symptoms,at which point the disease is in local progression or advanced stage,and the optimal opportunity for surgical intervention has been missed.Even after complete R0 resection,there is still a high recurrence rate,and the prognosis and survival rate are not optimistic.Different degrees of differentiation gastric cancer cells have a significantly different in growth rate,invasion and metastasis ability.According to Lauren classification of gastric cancer,diffuse gastric cancer has poor cell differentiation,high probability of distant metastasis and lymph node metastasis,and poor clinical prognosis.The purpose of this study is to explore the potential genes that can predict the prognosis of different types of gastric cancer by using bioinformatics methods,and provide a new idea for the clinical diagnosis and treatment of gastric cancer.Materials and methods: downloaded The GSE65524 dataset from GEO database,and the differentially expressed genes were screened and mapped by R software's "limma" and "survival" packages;the GO enrichment analysis and KEGG pathway enrichment analysis of differentially expressed genes were performed by David software.The protein interaction network of differentially expressed genes was constructed by bioinformatics tool STRING,and the visualization expression tool Cytoscape was used to screen the hub genes.Selected 40 patients with gastric cancer confirmed by postoperative pathology,used Immunohistochemistry to detect the protein expression of hub gene transcription in paraffin embedded samples.Total RNA was extracted from tissue samples,and the expression of hub genes in diffuse gastric cancer group and intestinal gastric cancer group was detected by q RT-PCR,analyzed the differences of the relative expression levels between the two groups.Finally,Kaplan-Meier plotter database was used to analyze the prognostic relationship of hub genes in gastric cancer.Results: After processing and screening,A total of 355 survival-related DEGs were selected according to specific screening criteria,of which 293 were associated with diffuse-type gastric cancer and 62 with intestinal-type gastric cancer.Gene Ontology analysis showed that the diffuse-type gastric cancer gene was mainly involved in the biological process of cell adhesion,mainly in the extracellular bodies,and its molecular function was mainly calcium binding,while the intestinal-type gastric cancer gene was mainly involved in the biological process of cell division,mainly in the nucleus,and its molecular function was protein binding.KEGG pathway analysis showed that diffuse-type gastric cancer genes were mainly involved in c GMP PKG signaling pathway,while intestinal-type gastric cancer genes were mainly involved in cell cycle pathway.Using protein?protein interaction networks and Cytoscape software,three hub genes were identified in diffuse-type gastric cancer associated DEGs,including angiotensinogen(AGT),C?X?C motif chemokine ligand 12(CXCL12)and adrenoceptor ?2(ADRB2),which may be the hub genes to induce the occurrence and development of diffuse-type gastric cancer.Immunohistochemical staining and reverse transcription quantitative PCR revealed that the expression levels of the three genes in diffuse-type gastric cancer samples were upregulated compared with in intestinal-type gastric cancer samples.Kaplan Meier survival analysis also indicated that a higher expression levels of AGT,CXCL12 and ADRB2 were associated with a poorer prognosis of patients with diffuse?type gastric cancer,suggesting that these genes have important research value in the occurrence and development of diffuse-type gastric cancer.Conclusion: In this study,we found that the expression of AGT,CXCL12 and ADRB2 might contribute to the progression of diffuse-type gastric cancer,and could serve as potential biomarkers or therapeutic targets for this disease. |
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