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Single-cell transcriptomic analysis suggests two molecularly distinct subtypes of intrahepatic cholangiocarcinoma
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 a...
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Published in: | Nature communications 2022-03, Vol.13 (1), Article 1642 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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
phl
) and peripheral small duct type (iCCA
pps
). S100P + SPP1− iCCA
phl
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
pps
. The transcription factor CREB3L1 is identified to regulate the S100P expression and promote tumor cell invasion. S100P-SPP1 + iCCA
pps
has significantly more SPP1
+
macrophage infiltration, less aggressiveness and better survival than S100P + SPP1− iCCA
phl
. Moreover, S100P-SPP1 + iCCA
pps
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.
The molecular classification and tumour microenvironment in intrahepatic cholangiocarcinoma (iCCA) need further characterisation. Here, the authors perform single cell RNA-sequencing from 14 pairs of iCCA tumours and non-tumour liver tissues and propose S100P and SPP1 as markers for patient classification. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-022-29164-0 |