PO.BCS01.02 · 生物信息与计算
通过单细胞核RNA测序鉴定化生性乳腺癌中独特的肿瘤生态系统
Unique tumor ecosystems in metaplastic breast cancer identified through single nucleus RNA sequencing
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
化生性乳腺癌(MBC)是一种罕见的侵袭性三阴性乳腺癌(TNBC)，占所有乳腺癌的比例不足1%。MBC患者接受与其他TNBC相似的治疗，但与其他TNBC患者相比，其预后始终更差、生存率更低。影响MBC治疗难治性的主要方面在于该肿瘤中肿瘤细胞向间充质/肉瘤样表型（如梭形细胞、软骨母细胞等）分化的异质性。本研究的目的是利用单细胞核RNA测序(snRNA)研究这些发生转分化的MBC肿瘤细胞及肿瘤微环境(TME)的变化，并与其他TNBC和正常乳腺组织进行比较。对于snRNA，我们在通过FACS去除游离RNA后，对每个肿瘤分析了5000-10,000个细胞核，并比较了来自MBC、TNBC和正常乳腺组织的组织样本。此外，我们还报告MBC与其他TNBC相比具有不同的髓系细胞状态比例，包括MBC中SIPA1L1髓系细胞肿瘤细胞群体的显著增加。我们还描述了在MBC中富集的、与正常乳腺和TNBC不同的新型成纤维细胞群体。总体而言，MBC的TME在内皮细胞、成纤维细胞和髓系细胞区室中也表现出增殖细胞数量的增加。在发生转分化的MBC肿瘤细胞中，我们还利用非负矩阵分解(NMF)分析定义了新型转录性元基因程序。总体而言，我们的数据首次以单细胞分辨率鉴定了这种罕见乳腺癌独特的肿瘤细胞程序和TME，并鉴定出定义其独特肿瘤生物学的潜在新细胞状态。
查看英文原文 English abstract
Metaplastic breast cancers (MBC) are rare, aggressive triple negative breast cancers (TNBC) that account for less than 1% of all breast cancers. Patients with MBCs are treated similarly to other TNBCs, however, consistently have a worse prognosis and decreased survival in comparison to other TNBC patients. The main aspect affecting MBCs treatment refractoriness is the heterogeneity of tumor cell differentiation in this tumor towards cells of mesenchymal/sarcoma like phenotype e.g. spindle cells, chondroblasts etc. The objective of this study was to investigate these transdifferentiated MBC tumor cells and tumor microenvironment (TME) changes in comparison to other TNBCs and normal breast tissues using single nucleus RNA sequencing (snRNA). For snRNA we profiled 5000-10,000 nuclei per tumor after running FACS to remove ambient RNA and compared tissue samples from MBCs, TNBC and normal breast tissues. Additionally, we also report that MBCs have different myeloid cell state proportions in comparison to other TNBCs, including a significant increased population of SIPA1L1 myeloid cells cancer cells in MBCs. We also describe novel fibroblast populations enriched in the MBC that are distinct from normal breast and TNBCs. Overall, the MBC TME also exhibits an increased number of proliferative cells in endothelial, fibroblast and myeloid cell compartments. In the transdifferentiated MBC cancer cells, we also define novel transcriptional metagene programs using non-negative matrix factorization (NMF) analysis. Collectively our data identifies the distinctive cancer cell programs and TME of this rare breast cancer for the first time at a single cell resolution and identifies potential new cell states that define it's unique tumor biology.
利益披露 Disclosure
A. Thennavan, None..
T. Tran, None.