Upregulated BAP31 Links to Poor Prognosis and Tumor Immune Microenvironment in Breast Cancer

BAP31表达上调与乳腺癌预后不良和肿瘤免疫微环境相关

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Abstract

BAP31, a transmembrane protein in the endoplasmic reticulum, is known for its oncogenic properties, but its role in immunotherapy is not well understood. While BAP31's involvement in liver, gastric, and cervical cancers has been documented, its role in pan-cancer immune regulation, particularly in breast cancer, remains unexplored. Using TCGA data, analysis via the Xiantao academic and GEPIA2 database showed that BAP31 upregulation correlates with advanced clinical stages and a poor prognosis. ROC analysis demonstrated BAP31's high accuracy in distinguishing cancerous tissue from normal tissues. Additionally, BAP31 expression is associated with CNV, methylation, TMB, and MSI. In breast cancer, TIMER database analysis revealed that BAP31 expression is inversely correlated with the infiltration levels of myeloid-derived suppressor cells (MDSCs), macrophages, T lymphocytes, B lymphocytes, and neutrophils. Additionally, we investigated the relationship between BAP31 and the expression of major histocompatibility complex (MHC) molecules and chemokine receptors utilizing the TISIDB database. LinkedOmics analysis demonstrated associations between BAP31 and various immune-inflammatory pathways, while also indicating a negative correlation between BAP31 expression and four critical pathways: extracellular matrix receptor interaction, focal adhesion, JAK-STAT signaling, and TGF-β signaling. Furthermore, loss-of-function experiments employing shRNA-mediated knockdown of BAP31 resulted in a marked reduction in cell proliferation and an increase in apoptosis in breast cancer cells, thereby confirming its role in tumor promotion. These findings suggest that BAP31 may serve as a promising prognostic biomarker and a potential target for immunotherapy in breast cancer.

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