Womens Cancer Research Center, UPMC Hillman Cancer Center, Magee Womens Research Institute, Pittsburgh, PA, 15213, USA.
School of Medicine, Tsinghua University, Beijing, 100084, China.
Sci Rep. 2018 May 8;8(1):7205. doi: 10.1038/s41598-018-25357-0.
Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.
浸润性小叶癌（ILC）是继浸润性导管癌（IDC）之后第二常见的乳腺癌组织学亚型。ILC 在许多组织学和临床特征上与 IDC 不同，例如单链生长、难以检测和频繁的晚期复发。为了了解涉及 ILC 临床特征的分子途径，我们使用 TCGA 数据比较了 luminal A ILC 和 luminal A IDC 的基因表达谱，并利用 METABRIC 中的样本作为验证数据集。在 ILC 中显著富集的顶级途径与免疫反应有关。与 IDC 相比，基于细胞类型特异性特征，ILC 显示出几乎所有类型免疫细胞的更高活性。相反，在 ILC 中富集程度较低的途径与蛋白质翻译和代谢有关，我们在细胞系中对其进行了功能验证。我们的研究中揭示的更高免疫活性突出了免疫疗法在 ILC 患者亚组中目前尚未探索的潜在应用。此外，众所周知的肿瘤休眠特征，即蛋白质翻译和代谢率较低，可能在 ILC 的晚期复发和乳房 X 线摄影和 PET 扫描中的低检测率中发挥作用。
