Hao Zhenzhen, Zhao Bo, Zhu Xiaoshuang, Zhang Wanting, Wang Bing
Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Int J Mol Sci. 2025 Jun 21;26(13):5975. doi: 10.3390/ijms26135975.
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.
BAP31是内质网中的一种跨膜蛋白,以其致癌特性而闻名,但其在免疫治疗中的作用尚不清楚。虽然已有文献记载BAP31参与肝癌、胃癌和宫颈癌的发生,但它在泛癌免疫调节中的作用,尤其是在乳腺癌中的作用,仍有待探索。利用TCGA数据,通过仙桃学术和GEPIA2数据库进行分析,结果显示BAP31的上调与临床晚期和不良预后相关。ROC分析表明BAP31在区分癌组织和正常组织方面具有很高的准确性。此外,BAP31的表达与CNV、甲基化、肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)有关。在乳腺癌中,TIMER数据库分析显示BAP31的表达与髓源性抑制细胞(MDSC)、巨噬细胞、T淋巴细胞、B淋巴细胞和中性粒细胞的浸润水平呈负相关。此外,我们利用TISIDB数据库研究了BAP31与主要组织相容性复合体(MHC)分子和趋化因子受体表达之间的关系。LinkedOmics分析表明BAP31与各种免疫炎症途径有关,同时也表明BAP31的表达与四个关键途径呈负相关,这四个途径分别是细胞外基质受体相互作用、粘着斑、JAK-STAT信号传导和TGF-β信号传导。此外,采用shRNA介导的BAP31敲低的功能丧失实验导致乳腺癌细胞的细胞增殖显著减少,凋亡增加,从而证实了其在肿瘤促进中的作用。这些发现表明,BAP31可能是一种有前景的预后生物标志物,也是乳腺癌免疫治疗的潜在靶点。