Oh Jung Hun, Pareja Fresia, Elkin Rena, Xu Kaiming, Norton Larry, Deasy Joseph O
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
NPJ Breast Cancer. 2025 Jan 29;11(1):8. doi: 10.1038/s41523-025-00725-y.
Using a novel unsupervised method to integrate multi-omic data, we previously identified a breast cancer group with a poor prognosis. In the current study, we characterize the biological features of this subgroup, defined as the high-risk group, using various data sources. Assessment of three published hypoxia signatures showed that the high-risk group exhibited higher hypoxia scores (p < 0.0001 in all three signatures), compared to the low-risk group. Our analysis of the immune cell composition using CIBERSORT and leukocyte fraction showed significant differences between the high and low-risk groups across the entire cohort, as well as within PAM50 subtypes. Within the basal subtype, the low-risk group had a statistically significantly higher spatial fraction of tumor-infiltrating lymphocytes (TILs) compared to the high-risk group (p = 0.0362). Our findings indicate that this subgroup with poor prognosis is driven by a distinct biological signature with high activation of hypoxia-related genes as well as a low number of TILs.
我们先前使用一种新型无监督方法整合多组学数据，鉴定出了一个预后不良的乳腺癌组。在当前研究中，我们使用各种数据源来描述这个被定义为高风险组的亚组的生物学特征。对三个已发表的缺氧特征的评估表明，与低风险组相比，高风险组表现出更高的缺氧评分（在所有三个特征中p < 0.0001）。我们使用CIBERSORT和白细胞分数对免疫细胞组成进行的分析表明，在整个队列以及PAM50亚型中，高风险组和低风险组之间存在显著差异。在基底亚型中，与高风险组相比，低风险组的肿瘤浸润淋巴细胞（TILs）空间分数在统计学上显著更高（p = 0.0362）。我们的研究结果表明，这个预后不良的亚组是由一种独特的生物学特征驱动的，该特征具有缺氧相关基因的高激活以及低数量的TILs。
