Comprehensive understanding of B7 family in gastric cancer: expression profile, association with clinicopathological parameters and downstream targets

Abstract

Objectives: B7 family members were identified as co-stimulators or co-inhibitors of the immune response and played important roles in cancer immunotherapy; however, their dysregulation in gastric cancer is still unclear. Methods: Data were obtained from TCGA and GTEX database. B7 mutations, association with DNA methylation and affected proteins were analyzed in cBioportal. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) project was studied by DAVID to find the downstream signaling pathway and important metabolic process, respectively. Protein-protein interaction network was analyzed in STRING and Cytoscape. A total of 160 paired specimens in tissue microarray from patients with gastric cancer were used to detect the expression levels of seven B7 family members via immunohistochemical analysis. Results: Bioinformatics studies revealed dysregulation of B7 members in gastric cancer. Gene and protein alteration were found in B7 family members. Furthermore, DNA methylation and gene alteration may be both involved in B7 member dysregulation in gastric cancer. Importantly, the high expression of B7-H6 is associated with good overall patient 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. The low expression of B7-1 and high expression of B7-H3 and B7-H7 were validated by IHC staining. Conclusions: Our results provide insight into B7 family member expression in gastric cancer and stress their importance in stomach tumorigenesis, which may be beneficial for designing future cancer treatments.

Dual role of B7‐H6 as a novel prognostic marker in hepatocellular carcinoma

“…Different research groups showed that B7‐H6 has no significant diagnostic or prognostic value in non‐small cell lung cancer and gastric cancer (26, 27). With the data from TCGA and GTEX database, Li and his colleagues revealed that the high expression of B7‐H6 was associated with good overall patient survival in gastric cancer (25). Cao et al recently showed that expression of B7‐H6 in chronic myeloid leukemia (CML) was negatively correlated with the copy number of fusion gene BCR‐ABL1, and furthermore, the patients with high B7‐H6 level had significantly longer progression‐free survival than those with low B7‐H6 expression level (28).…”

“…Studies have reported that the expression of B7‐H6 is related to the metastasis of some cancers, and the B7‐H6 expression is negatively correlated with the overall survival (OS) rate of ovarian cancer, breast cancer, brain tumor, esophageal squamous cell carcinoma, cervical cancer, and esophageal squamous cell carcinoma (17, 19–24). However, the situation is not always the same, and it was found that the higher expression of B7‐H6 predicted favorable overall patient survival in gastric cancer (25). Moreover, the clinical significance of B7‐H6 in HCC patients remains uncertain.…”

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

“…Different B7 molecules have either positive or negative co-stimulatory signals while modulating immune cell responses (Table 1) [4,5]. Immune checkpoints, such as PD-1, PD-L1, PD-L2, and CTLA4, are molecules holding many receptor-ligand interactions to evade the immune system and facilitate proliferation.…”

m5C RNA Methylation Primarily Affects the ErbB and PI3K–Akt Signaling Pathways in Gastrointestinal Cancer

“…Differential proteins are shown by the volcano plot using GraphPad Prism 7. The selected proteins from this criterion were used to predict pathways by two conditions: (a) the sum of altered protein in each pathway and (b) the statistical P value score of significant pathway ( Li D. et al, 2020 ). Finally, the screened differential proteins were used to predict the pathway in the DAVID function annotation tool 4 .…”