Zhou Xuehao, Wang Yu, Xu Qingling, Ao Xiang, Chen Mengmeng, Zhang Bingqiang, Liu Ying
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, Shandong, 266071, China.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
BMC Cancer. 2025 Jul 24;25(1):1205. doi: 10.1186/s12885-025-14576-0.
BACKGROUND: The B-aggressive lymphoma (BAL) proteins, including BAL1, BAL2, and BAL3, constitute a conserved protein family characterized by their N-terminal macro domains and putative C-terminal poly (ADP-ribose) polymerase (PARP) active site. Dysregulation of BALs has been closely associated with the progression of various cancers. However, there is limited understanding of their precise expression profile, prognostic significance, and role in breast cancer (BC). METHODS: The expression patterns of BALs were evaluated utilizing multiple databases, including Ualcan, Gene Set Cancer Analysis (GSCA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and Gene Expression Profiling Interactive Analysis (GEPIA). The prognostic significance of BALs was assessed via Kaplan-Meier plotter analysis. Furthermore, the potential mechanisms underlying the contribution of BC progression were predicted through GO and KEGG pathway enrichment analysis. Additionally, the effect of BALs on the malignant behaviors of BC cells was determined using CCK-8 assay, Transwell assay, and TUNEL assay. RESULTS: The data revealed that the expression levels of both BAL1 and BAL2 were upregulated in BC, whereas no significant change was observed for BAL3. Survival analysis demonstrated a strong association between the overexpression of both BAL1 and BAL2 and favorable prognosis in patients with various subtypes of BC, including estrogen receptor (ER)-positive, ER-negative, Basal, luminal B, HER2-, and HER2 + subtypes. Additionally, the knockdown of BAL1 and BAL2 inhibited the proliferation and migration of BC cells while facilitating apoptosis. CONCLUSIONS: These findings suggest that both BAL1 and BAL2 hold great potential as significant prognostic biomarkers and therapeutic targets for patients with BC.
背景:B 侵袭性淋巴瘤(BAL)蛋白,包括 BAL1、BAL2 和 BAL3,构成了一个保守的蛋白家族,其特征在于它们的 N 端宏观结构域和假定的 C 端多聚(ADP - 核糖)聚合酶(PARP)活性位点。BAL 蛋白的失调与多种癌症的进展密切相关。然而,人们对它们在乳腺癌(BC)中的精确表达谱、预后意义和作用了解有限。 方法:利用多个数据库评估 BAL 蛋白的表达模式,包括 Ualcan、基因集癌症分析(GSCA)、检索相互作用基因/蛋白的搜索工具(STRING)和基因表达谱交互式分析(GEPIA)。通过 Kaplan - Meier 绘图仪分析评估 BAL 蛋白的预后意义。此外,通过 GO 和 KEGG 通路富集分析预测 BC 进展的潜在机制。另外,使用 CCK - 8 试验、Transwell 试验和 TUNEL 试验确定 BAL 蛋白对 BC 细胞恶性行为的影响。 结果:数据显示,BC 中 BAL1 和 BAL2 的表达水平均上调,而 BAL3 未观察到显著变化。生存分析表明,BAL1 和 BAL2 的过表达与包括雌激素受体(ER)阳性、ER 阴性乳腺癌、基底样、管腔 B 型、HER2 阴性和 HER2 阳性亚型在内的各种 BC 亚型患者的良好预后密切相关。此外,敲低 BAL1 和 BAL2 可抑制 BC 细胞的增殖和迁移,同时促进细胞凋亡。 结论:这些发现表明,BAL1 和 BAL2 作为 BC 患者重要的预后生物标志物和治疗靶点具有巨大潜力。
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