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Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ
Cancer Research ( IF 12.5 ) Pub Date : 2022-07-19 , DOI: 10.1158/0008-5472.can-22-0090
Momoko Tokura 1, 2 , Jun Nakayama 1 , Marta Prieto-Vila 3 , Sho Shiino 4 , Masayuki Yoshida 5 , Tomofumi Yamamoto 1 , Naoaki Watanabe 1 , Shin Takayama 4 , Yutaka Suzuki 6 , Koji Okamoto 7 , Takahiro Ochiya 3 , Takashi Kohno 2, 8 , Yasushi Yatabe 5 , Akihiko Suto 4 , Yusuke Yamamoto 1
Affiliation  

Ductal carcinoma in situ (DCIS) is a precursor to invasive breast cancer. The frequency of DCIS is increasing because of routine mammography; however, the biological features and intratumoral heterogeneity of DCIS remain obscure. To address this deficiency, we performed single-cell transcriptomic profiling of DCIS and invasive ductal carcinoma (IDC). DCIS was found to be composed of several transcriptionally distinct subpopulations of cancer cells with specific functions. Several transcripts, including long noncoding RNAs, were highly expressed in IDC compared with DCIS and might be related to the invasive phenotype. Closeness centrality analysis revealed extensive heterogeneity in DCIS, and the prediction model for cell-to-cell interactions implied that the interaction network among luminal cells and immune cells in DCIS was comparable with that in IDC. In addition, transcriptomic profiling of HER2+ luminal DCIS indicated HER2 genomic amplification at the DCIS stage. These data provide novel insight into the intratumoral heterogeneity and molecular features of DCIS, which exhibit properties similar to IDC. Significance: Investigation of the molecular features of ductal carcinoma in situ at single cell resolution provides new insights into breast cancer biology and identifies candidate therapeutic targets and diagnostic biomarkers.

中文翻译:

单细胞转录组分析揭示导管原位癌的瘤内异质性和分子特征

导管原位癌(DCIS)是浸润性乳腺癌的前兆。由于常规乳房 X 光检查,导管原位癌 (DCIS) 的发生率正在增加;然而,DCIS 的生物学特征和瘤内异质性仍然不清楚。为了解决这一缺陷,我们对 DCIS 和浸润性导管癌 (IDC) 进行了单细胞转录组分析。研究发现导管原位癌 (DCIS) 由几个转录上不同且具有特定功能的癌细胞亚群组成。与 DCIS 相比,IDC 中的一些转录物(包括长非编码 RNA)高表达,可能与侵袭表型有关。紧密中心性分析揭示了 DCIS 中广泛的异质性,细胞间相互作用的预测模型表明,DCIS 中的管腔细胞和免疫细胞之间的相互作用网络与 IDC 中的具有可比性。此外,HER2+ luminal DCIS 的转录组分析表明 HER2 基因组在 DCIS 阶段扩增。这些数据为 DCIS 的瘤内异质性和分子特征提供了新的见解,其表现出与 IDC 相似的特性。意义:以单细胞分辨率研究原位导管癌的分子特征,为乳腺癌生物学提供了新的见解,并确定了候选治疗靶点和诊断生物标志物。这些数据为 DCIS 的瘤内异质性和分子特征提供了新的见解,其表现出与 IDC 相似的特性。意义:以单细胞分辨率研究原位导管癌的分子特征,为乳腺癌生物学提供了新的见解,并确定了候选治疗靶点和诊断生物标志物。这些数据为 DCIS 的瘤内异质性和分子特征提供了新的见解,其表现出与 IDC 相似的特性。意义:以单细胞分辨率研究原位导管癌的分子特征,为乳腺癌生物学提供了新的见解,并确定了候选治疗靶点和诊断生物标志物。
更新日期:2022-07-19
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