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

• Published in: Nature communications 2022-03, Vol.13 (1), p.1642-1642
• Main Authors: Song, Guohe, 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, Ya, Ji, Yuan, Zhou, Jian, Fan, Jia, Zhang, Xiaoming, Xi, Ruibin, Gao, Qiang
• Format: Article
• Language: English
• Subjects: Bile Duct Neoplasms - genetics; Bile Ducts, Intrahepatic; CD8-Positive T-Lymphocytes - metabolism; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Humans; Transcriptome; Tumor Microenvironment - genetics
• ISSN: 2041-1723
• DOI: 10.1038/s41467-022-29164-0

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 (iCCA ) and peripheral small duct type (iCCA ). S100P + SPP1- iCCA 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 + iCCA . The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCA has significantly more SPP1 macrophage infiltration, less aggressiveness and better survival than S100P + SPP1- iCCA . Moreover, S100P-SPP1 + iCCA 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.