Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, Section for Pathology, University of Bergen, Bergen, N-5021, Norway.
Department of Pathology, Haukeland University Hospital, Bergen, N-5021, Norway.
Nat Commun. 2023 Jun 22;14(1):3724. doi: 10.1038/s41467-023-39287-7.
Cancers are often associated with hypoxia and metabolic reprogramming, resulting in enhanced tumor progression. Here, we aim to study breast cancer hypoxia responses, focusing on secreted proteins from low-grade (luminal-like) and high-grade (basal-like) cell lines before and after hypoxia. We examine the overlap between proteomics data from secretome analysis and laser microdissected human breast cancer stroma, and we identify a 33-protein stromal-based hypoxia profile (33P) capturing differences between luminal-like and basal-like tumors. The 33P signature is associated with metabolic differences and other adaptations following hypoxia. We observe that mRNA values for 33P predict patient survival independently of molecular subtypes and basic prognostic factors, also among low-grade luminal-like tumors. We find a significant prognostic interaction between 33P and radiation therapy.
癌症通常与缺氧和代谢重编程有关，导致肿瘤进展增强。在这里，我们旨在研究乳腺癌缺氧反应，重点研究低级别（管腔样）和高级别（基底样）细胞系在缺氧前后分泌的蛋白质。我们检查了分泌组分析的蛋白质组学数据与激光微切割的人类乳腺癌基质之间的重叠，并确定了一个基于基质的 33 种蛋白质缺氧特征（33P），该特征捕捉了管腔样和基底样肿瘤之间的差异。33P 特征与缺氧后代谢差异和其他适应有关。我们观察到，33P 的 mRNA 值可独立于分子亚型和基本预后因素预测患者的生存，在低级别管腔样肿瘤中也是如此。我们发现 33P 和放射治疗之间存在显著的预后相互作用。
