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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.

SUBMITTER: Li D

PROVIDER: S-EPMC6990920 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Li Dan D Xiang Shixin S Shen Jing J Xiao Mingtao M Zhao Yueshui Y Wu Xu X Du Fukuan F Ji Huijiao H Li Mingxing M Zhao Qijie Q Kaboli Parham Jabbarzadeh PJ Yang Xiao X Xiao Zhangang Z Qin Bo B Wen Qinglian Q

International journal of biological sciences 20200101 4

<b>Objectives:</b> 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. <b>Methods:</b> 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 ...[more]

PMID: 32025206

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Project description:Background: Gastric cancer (GC) is one of the most common and poor prognosis malignancy in the world. The Family with sequence similarity 83 (FAM83) comprises of eight members of A-H. Accumulating evidence confirmed important roles for FAM83 family in tumorigenesis and progression. However, the prognostic values of FAM83 family in GC still have not been clarified. Methods: ONCOMINE, UALCAN, GEPIA, THE HUMAN PROTEIN ATLAS, Kaplan-Meier Plotter, cBioPortal, DAVID, STRING and TIMER databases and R software were adopted in this study. Results: In this study, we demonstrated that the mRNA levels of FAM83 B/C/D/H were significantly up-regulated in stomach adenocarcinoma (STAD), but the protein level of FAM83G/H were remarkable lowly in STAD. Next, FAM83C/D/G/H were significantly associated with tumor stages in STAD patients. Then, the mutation rate of FAM83 family members in STAD patients was 46%, and the highest mutation rate was FAM83H (23%). Furthermore, the functions of FAM83 family and their 259 co-expression genes were primarily related to Shigellosis, RNA degradation and Ribosome biogenesis in eukaryotes pathway. Besides, we have established the prognostic model of FAM83 family in STAD, including the prognostic model of STAD patients (FAM83C/D/G), STAD with lymph node metastasis (FAM83C/D/G/H) and STAD with ERBB2 high expression (FAM83G/H). FAM83C/D high expression with a poor prognosis, while FAM83G/H high expression with a favorable prognosis of STAD. Additionally, we found that the expression of FAM83C/D/G/H were significantly correlated with the infiltration of six types of immune cells [B cells, CD8+T cells, CD4+T cells, macrophages and Myeloid dendritic cells (DC)], whereas CD4+T cells and Macrophage cells have higher risk scores (HR > 1) when FAM83C lowly expression and FAM83D highly expression. The risk score of NK cells was significantly reduced when FAM83G lowly expression and FAM83H highly expression (HR < 1). Conclusion: These findings suggested that FAM83C/D/G/H might play key roles in STAD tumorigenesis and progression, and FAM83C/D might be risk factors but FAM83G/H might be favorable prognostic factors for STAD patients. In addition, CD4+T cells and Macrophage cells may be the promoters of FAM83D in progression of STAD, while NK cells may promote the protective effect of FAM83H on STAD patients.

Dataset Information

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

Publications

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

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