| Objectives: B7 family members were identified as co-stimulators or coinhibitors of the immune response.The B7 protein family not only binds to the signals generated by the corresponding receptors and plays an important role in regulating T cell activation and effector cytokine secretion,but also plays an important role in immune response.However,until now,the abnormal regulation of B7 family members in gastric cancer remains unclear.Therefore,further study on the biological role of these molecules in gastric cancer will be helpful to understand the pathogenesis of diseases caused by abnormal T cell activation,and provide a new direction for tumor immunotherapy.In this study,we used bioinformatics methods to explore the differences in gene expression levels of the B7 family in gastric cancer,and the relationship between its expression level and various clinicopathological parameters of gastric cancer.In addition,we conducted KEGG enrichment analysis and GO analysis on differential proteins of the B7 family,and finally identified a downstream target for further analysis.Besides,we also combined relevant clinical tissue samples to analyze the expression differences of B7 family members in patients with gastric cancer,and explored its clinical significance in tumor immunotherapy.Methods: Transcriptome data were collected from TCGA and GTEX databases,including 373 gastric cancer tissue samples and 205 normal samples.In addition,clinical follow-up data can be obtained from the TCGA database.We analyzed the mutations of B7 family members in gastric cancer in the c Bio Portal database,the relationship between the expression levels of B7 family members and DNA methylation and copy number,and the proteins affected by B7 family members.Besides,we also used Graph Pad Prism 7,SPSS 22.0 and other software for data statistical analysis.the DAVID database can also be used to study the Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment and gene ontology(GO),which we used to analyze the downstream signaling pathways and important metabolic processes of B7 family members,respectively.At the same time,we conducted protein interaction network analysis in the STRING database and Cytoscape software.R project,a tool for statistical calculation and statistical mapping,was used to determine the correlation with downstream proteins.Finally,the expression levels of B7 family members were detected by immunohistochemical(IHC)analysis using tissue microarray from 160 pairs of gastric cancer patients.Results: Bioinformatics analysis showed that the B7 family function was abnormally expressed in gastric cancer.DNA methylation and copy number variation may be related to abnormal expression of B7 members in gastric cancer.More importantly,higher B7-H6 gene expression was significantly associated with better overall survival.B7 family members primarily affect the EGFR tyrosine kinase inhibitor resistance signaling pathway in gastric cancer and TP53 may be an important target of the family.We further confirmed the low expression of B7-1 gene and the high expression of B7-H3 and B7-H7 genes in gastric cancer by IHC staining.Conclusions: Results revealed that most members of the B7 family are abnormally expressed in gastric cancer,and found that the B7 family may play an effect in gastric cancer through the EGFR tyrosine kinase inhibitor resistance signaling pathway.In addition,the expression level of B7-H6 gene has an important impact on the survival of gastric cancer patients,which emphasizes the importance of B7 family members in the occurrence of gastric cancer,which may help provide future cancer treatment strategies. |
