Single-Cell Transcriptome Profiling Reveals Intratumoral Heterogeneity and Molecular Features of Ductal Carcinoma In Situ

导管癌 转录组 生物 乳腺癌 表型 原位 癌症研究 肿瘤异质性 计算生物学 癌症 病理 医学 基因 遗传学 基因表达 化学 有机化学
作者
Momoko Tokura,Jun Nakayama,Marta Prieto‐Vila,Sho Shiino,Masayuki Yoshida,Tomofumi Yamamoto,Naoaki Watanabe,Shin Takayama,Yutaka Suzuki,Koji Okamoto,Takahiro Ochiya,Takashi Kohno,Yasushi Yatabe,Akihiko Suto,Yusuke Yamamoto
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:82 (18): 3236-3248 被引量:14
标识
DOI:10.1158/0008-5472.can-22-0090
摘要

Abstract 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.
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