Int J Biol Sci 2020; 16(4):568-582. doi:10.7150/ijbs.39769

Research Paper

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

Dan Li1*, Shixin Xiang2,3*, Jing Shen2,3*, Mingtao Xiao2,3, Yueshui Zhao2, Xu Wu2,3, Fukuan Du2,3, Huijiao Ji2,3, Mingxing Li2,3, Qijie Zhao2, Parham Jabbarzadeh Kaboli2,3, Xiao Yang2, Zhangang Xiao2,3✉, Bo Qin4✉, Qinglian Wen1✉

1. Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
2. Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, PR China.
3. South Sichuan Institute of Translational Medicine, Luzhou, 646000, Sichuan, PR China.
4. Shenzhen Aier Aye Hospital, Shenzhen, 518032, Guangdong, PR China
*These authors contributed equally to this work

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Citation:
Li D, Xiang S, Shen J, Xiao M, Zhao Y, Wu X, Du F, Ji H, Li M, Zhao Q, Kaboli PJ, Yang X, Xiao Z, Qin B, Wen Q. Comprehensive understanding of B7 family in gastric cancer: expression profile, association with clinicopathological parameters and downstream targets. Int J Biol Sci 2020; 16(4):568-582. doi:10.7150/ijbs.39769. Available from http://www.ijbs.com/v16p0568.htm

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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.

Keywords: B7 family members, gastric cancer, bioinformatics, PI3K-AKT signaling pathway