Comprehensive Analysis Reveals Distinct Immunological and Prognostic Characteristics of CD276/B7-H3 in Pan-Cancer

BACKGROUND: CD276 (also known as B7-H3), a newly discovered immunoregulatory protein that belongs to the B7 family, is a significant and attractive target for cancer immunotherapy. Existing evidence demonstrates its pivotal role in the tumorigenesis of some cancers. However, there still lacks a systematic and comprehensive pan-cancer analysis of the role of CD276 in tumor immunology and prognosis. METHODS: We explored and validated the mRNA and protein expression levels of CD276 in multiple tumors through public databases and clinical tissues specimens. The Univariate Cox regression analysis and Kaplan–Meier analysis were applied to assess the prognostic value of CD276. The correlation between CD276 expression and clinical characteristics and immunological features in diverse tumors was also explored. GSEA was performed to illuminate the biological function and involved pathways of CD276. Moreover, the CellMiner database was used to interpret the relationship between CD276 and multiple chemotherapeutic agents. CCK-8 assay was performed to validate the biological function of CD276 in vitro. RESULTS: In general, CD276 was differentially expressed between most tumor tissues and their corresponding normal tissues. Higher expression levels of CD276 were associated with poorer survival outcomes in most tumor cohorts from TCGA. There was a close correlation between CD276 expression and clinical features, the infiltration levels of specific immune cells, immune subtypes, TMB, MSI, MMR, recognized immunoregulatory genes and drug sensitivity across diverse human cancers. The scRNA-seq data analysis further revealed that CD276 was mainly expressed on the tumor infiltrating macrophages. Additionally, in vitro experiments showed that knockdown of CD276 inhibited the proliferation of ovarian cancer (OV) and cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) cell lines. CONCLUSION: CD276 is a potent biomarker for predicting the prognosis and immunological features in some tumors, and it may play a critical role in the tumor immune microenvironment (TIME) through macrophage-associated signaling.