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Updated: Dec 29, 2025
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Comprehensive understanding of B7 family in gastric cancer: expression profile, association with clinicopathological
Dan Li1, Shixin Xiang2,3, Jing Shen2,3
1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
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.
Insights
B7 family members are dysregulated in gastric cancer, impacting immune responses and tumorigenesis. High B7-H6 expression correlates with better patient survival, suggesting therapeutic potential.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- B7 family proteins regulate immune responses and are crucial in cancer immunotherapy.
- Dysregulation of B7 family members in gastric cancer remains poorly understood.
- Gastric cancer is a significant global health concern with complex underlying mechanisms.
Purpose of the Study:
- To investigate the role and expression patterns of B7 family members in gastric cancer.
- To identify potential molecular mechanisms, including DNA methylation and gene alterations, contributing to B7 dysregulation.
- To explore the association of B7 family members with patient survival and therapeutic resistance pathways.
Main Methods:
- Utilized TCGA and GTEX databases for bioinformatics analysis.
- Analyzed B7 mutations, DNA methylation, and protein interactions using cBioportal, DAVID, STRING, and Cytoscape.
- Validated expression levels of key B7 members (B7-1, B7-H3, B7-H6, B7-H7) in 160 gastric cancer specimens via immunohistochemical analysis.
Main Results:
- Bioinformatic analyses revealed significant dysregulation of B7 family members in gastric cancer.
- Both gene alterations and DNA methylation appear to contribute to B7 member dysregulation.
- High expression of B7-H6 was linked to improved overall patient survival.
- B7 family members were found to influence the EGFR tyrosine kinase inhibitor resistance pathway, with TP53 identified as a potential target.
- Immunohistochemistry confirmed low B7-1 and high B7-H3 and B7-H7 expression in gastric tumors.
Conclusions:
- B7 family members play a critical role in gastric cancer development and progression.
- Expression patterns of B7 family members, particularly B7-H6, have prognostic significance.
- Understanding B7 family member dysregulation offers potential avenues for novel gastric cancer therapeutic strategies.
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