Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma
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Published:2022-03-28
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Song GuoheORCID, Shi Yang, Meng Lu, Ma Jiaqiang, Huang Siyuan, Zhang Juan, Wu Yingcheng, Li Jiaxin, Lin Youpei, Yang Shuaixi, Rao Dongning, Cheng Yifei, Lin Jian, Ji Shuyi, Liu Yuming, Jiang Shan, Wang Xiaoliang, Zhang Shu, Ke Aiwu, Wang Xiaoying, Cao YaORCID, Ji YuanORCID, Zhou JianORCID, Fan JiaORCID, Zhang XiaomingORCID, Xi RuibinORCID, Gao QiangORCID
Abstract
AbstractIntrahepatic 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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