Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma

Guohe Song, Yang Shi, Lu Meng, Jiaqiang Ma, Siyuan Huang, Juan Zhang, Yingcheng Wu, Jiaxin Li, Youpei Lin, Shuaixi Yang, Dongning Rao, Yifei Cheng, Jian Lin, Shuyi Ji, Yuming Liu, Shan Jiang, Xiaoliang Wang, Shu Zhang, Aiwu Ke, Xiaoying Wang, Ya Cao, Yuan Ji, Jian Zhou, Jia Fan (), Xiaoming Zhang (), Ruibin Xi () and Qiang Gao ()
Additional contact information
Guohe Song: Fudan University
Yang Shi: Peking University
Lu Meng: Institut Pasteur of Shanghai, Chinese Academy of Sciences
Jiaqiang Ma: Fudan University
Siyuan Huang: Peking University
Juan Zhang: Fudan University
Yingcheng Wu: Fudan University
Jiaxin Li: Peking University
Youpei Lin: Fudan University
Shuaixi Yang: Fudan University
Dongning Rao: Fudan University
Yifei Cheng: Fudan University
Jian Lin: Fudan University
Shuyi Ji: Fudan University
Yuming Liu: Fudan University
Shan Jiang: Institut Pasteur of Shanghai, Chinese Academy of Sciences
Xiaoliang Wang: Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University
Shu Zhang: Fudan University
Aiwu Ke: Fudan University
Xiaoying Wang: Fudan University
Ya Cao: Central South University
Yuan Ji: Fudan University
Jian Zhou: Fudan University
Jia Fan: Fudan University
Xiaoming Zhang: Institut Pasteur of Shanghai, Chinese Academy of Sciences
Ruibin Xi: Peking University
Qiang Gao: Fudan University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Intrahepatic cholangiocarcinoma (iCCA) is a highly heterogeneous cancer with limited understanding of its classification and tumor microenvironment. Here, by performing single-cell RNA sequencing on 144,878 cells from 14 pairs of iCCA tumors and non-tumor liver tissues, we find that S100P and SPP1 are two markers for iCCA perihilar large duct type (iCCAphl) and peripheral small duct type (iCCApps). S100P + SPP1− iCCAphl has significantly reduced levels of infiltrating CD4+ T cells, CD56+ NK cells, and increased CCL18+ macrophages and PD1+CD8+ T cells compared to S100P-SPP1 + iCCApps. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCApps has significantly more SPP1+ macrophage infiltration, less aggressiveness and better survival than S100P + SPP1− iCCAphl. Moreover, S100P-SPP1 + iCCApps harbors tumor cells at different status of differentiation, such as ALB + hepatocyte differentiation and ID3+ stemness. Our study extends the understanding of the diversity of tumor cells in iCCA.

Date: 2022
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DOI: 10.1038/s41467-022-29164-0

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