文章：

基于公开数据验证的三阴性乳腺癌基底样亚型蛋白质组学特征

A Validated Proteomic Signature of Basal-like Triple-Negative Breast Cancer Subtypes Obtained from Publicly Available Data

原文发布日期：8 August 2025

DOI: 10.3390/cancers17162601

类型: Article

开放获取: 是

英文摘要：

Background: Basal-like breast cancer (BLBC) is a highly aggressive molecular subtype characterized by the strong expression of a gene cluster found in the basal or outer epithelial layer of the adult mammary gland. Patients with BLBC typically face a poor prognosis, with a shorter disease-free period and overall survival. Methods: In this study, we explored the proteomic profiles of BLBC patients using publicly available data from two large cohorts of breast cancer patients. By integrating cluster analysis, predictive modeling, protein differential abundance expression, and network analysis, we identified and validated the presence of two distinct subgroups, characterized by 256 upregulated and 99 downregulated proteins. Results: We report the upregulation of spliceosome components, especially SNRPG and its partners (BUD13, CWC15, SNRNP70, ZMAT12), indicating altered splicing activity between TNBC subgroups. Collagen proteins (COL1A1, COL1A2, COL3A1, COL11A1) were associated with tumor progression and metastasis. Proteins in the CCT complex and microtubule-associated proteins (TUBA1C, TUBB) were linked to cytoskeletal structure and chemotherapy resistance. Aminoacyl-tRNA synthetases (DARS1, IARS1, KARS1) may also play a role in TNBC development. Conclusions: These findings suggest the existence of novel molecular signatures that could improve TNBC classification, prognosis, and potential therapeutic targeting.

摘要翻译： 

背景：基底样乳腺癌是一种高度侵袭性的分子亚型，其特征是强烈表达在成人乳腺基底或外层上皮细胞中发现的基因簇。基底样乳腺癌患者通常预后较差，无病生存期和总生存期较短。方法：在本研究中，我们利用两个大型乳腺癌患者队列的公开数据，探索了基底样乳腺癌患者的蛋白质组学特征。通过整合聚类分析、预测建模、蛋白质差异丰度表达和网络分析，我们识别并验证了两个不同的亚组，其特征为256个上调蛋白和99个下调蛋白。结果：我们发现剪接体成分（尤其是SNRPG及其伴侣蛋白BUD13、CWC15、SNRNP70、ZMAT12）的上调，表明三阴性乳腺癌亚组间存在剪接活性的改变。胶原蛋白（COL1A1、COL1A2、COL3A1、COL11A1）与肿瘤进展和转移相关。CCT复合物中的蛋白质及微管相关蛋白（TUBA1C、TUBB）与细胞骨架结构和化疗耐药性有关。氨酰-tRNA合成酶（DARS1、IARS1、KARS1）也可能在三阴性乳腺癌的发展中发挥作用。结论：这些发现表明存在新的分子特征，可能有助于改善三阴性乳腺癌的分类、预后评估及潜在治疗靶点的开发。

原文链接：

A Validated Proteomic Signature of Basal-like Triple-Negative Breast Cancer Subtypes Obtained from Publicly Available Data