Comprehensive analysis of BTN3A1 in cancers: mining of omics data and validation in patient samples and cellular models

Abstract

Butyrophilin 3A1 (BTN3A1), a major histocompatibility complex (MHC)-associated gene that encodes a membrane protein with 2 extracellular immunoglobulin domains and an intracellular B30.2 domain, is critical in T-cell activation and adaptive immune response. Here, the expression of BTN3A1 in cancers was analyzed in 8 databases comprising 86,733 patients of 33 cancers and the findings were validated in patient samples and cell models. We showed that BTN3A1 was expressed in most cancers, and its expression level was strongly correlated with clinical outcome of 13 cancers. Mutations of BTN3A1 were detected, and the mutations were distributed throughout the entire gene. Gene set enrichment analysis (GSEA) showed that BTN3A1 co-expression genes and interacting proteins were enriched in immune regulation related pathways. BTN3A1 was associated with tumor infiltrating immune cells and was co-expressed with multiple immune checkpoints in patients with breast cancer (BRCA) and non-small cell lung cancer (NSCLC). We reported that BTN3A1 was downregulated in 46 of 65 (70.8%) NSCLCs, and its expression level was inversely associated with clinical outcome of the patients. BTN3A1 in tumor samples was lower than in counterpart normal tissues in 31 of 38 (81.6%) BRCAs. Bioinformatics analyses showed that BTN3A1 could be a target gene of transcription factor Spi-1 proto-oncogene (SPI1), and our "wet" experiments showed that ectopic expression of SPI1 upregulated, whereas silencing of SPI1 downregulated, BTN3A1 expression in cells. These results suggest that

Genomic Biomarker Heterogeneities between SARS-CoV-2 and COVID-19

“…EPSTI1 has been found to be related to breast cancer, oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LSCC) [ 49 ], which may link COVID-19 to what has been found in the complication of mammograms [ 13 ]. Liang et al (2021) [ 50 ] suggested that BTN3A1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLCs and BRCAs. A confirmed Hypothesis 2 may help further explore whether these genes reported in the literature are truly effective, as suggested in the literature.…”

Comprehensive glycoprofiling of oral tumours associatesN-glycosylation with lymph node metastasis and patient survival

“…One of the five Glycan 40a-carrying glycopeptides belongs to BTN3A1 (butyrophilin subfamily 3 member A1 or CD277) and was identified to associate with lymph node status. BTN3A1 plays a well-known role in T-cell activation and in the adaptive immune response, and altered BTN3A1 expression has been reported in different human cancers including in head and neck squamous cell carcinoma and in breast cancer ( 61 ). Remarkably, BTN3A1 was not detected in our OSCC proteome profile, Figure 7B, but only identified in HILIC-enriched glycoproteome analysis, highlighting the importance of employing multi-omics approaches to obtain a comprehensive coverage and holistic insights in the disease complexity and dynamics.…”

Genomic Biomarker Heterogeneities Between SARS-CoV-2 and COVID-19

“…EPSTI1 has been found related to breast cancer and oral squamous cell carcinoma (OSCC) and lung squamous cell carcinoma (LSCC) 35 , which may link COVID-19 to what has been found in mammograms complication 13 . Liang et al (2021) 36 suggests that BTN3A1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLCs and BRCAs. However, all of these findings have not been confirmed.…”