Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.
Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma.
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DOI：
10.1038/s41467-022-29164-0
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发表时间：
2022-03-28
影响因子：
16.6
通讯作者：
Gao Q
中科院分区：
文献类型：
--
作者：
Song G;Shi Y;Meng L;Ma J;Huang S;Zhang J;Wu Y;Li J;Lin Y;Yang S;Rao D;Cheng Y;Lin J;Ji S;Liu Y;Jiang S;Wang X;Zhang S;Ke A;Wang X;Cao Y;Ji Y;Zhou J;Fan J;Zhang X;Xi R;Gao Q
肝内胆管癌（iCCA）是一种高度异质性的肿瘤，对其分类和肿瘤微环境的了解有限。本研究通过对14对iCCA肿瘤和非肿瘤肝组织的144,878个细胞进行单细胞RNA测序，发现S100P和SPP1是iCCA门周大管型（iCCAphl）和外周小管型（iCCApps）的两个标记物。与S100P-SPP1 + iCCApps相比，S100P + SPP1−iCCAphl显著降低CD4+ T细胞、CD56+ NK细胞的浸润水平，增加CCL18+巨噬细胞和PD1+CD8+ T细胞的浸润水平。发现转录因子CREB3L1调节S100P表达，促进肿瘤细胞侵袭。与S100P + SPP1−iCCAphl相比，S100P-SPP1 + iCCApps的SPP1+巨噬细胞浸润量明显增加，侵袭性明显降低，生存率明显提高。此外，S100P-SPP1 + iCCApps还含有不同分化状态的肿瘤细胞，如ALB +肝细胞分化和ID3+干细胞分化。我们的研究扩展了对iCCA肿瘤细胞多样性的认识。肝内胆管癌（iCCA）的分子分类和肿瘤微环境有待进一步研究。在这里，作者对14对iCCA肿瘤和非肿瘤肝组织进行单细胞rna测序，并提出S100P和SPP1作为患者分类的标记物。
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. 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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影响因子：
16.6
作者：
Chen Z;Zhou L;Liu L;Hou Y;Xiong M;Yang Y;Hu J;Chen K
通讯作者：
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影响因子：
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作者：
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影响因子：
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通讯作者：
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影响因子：
30.3
作者：
Denard B;Seemann J;Chen Q;Gay A;Huang H;Chen Y;Ye J
通讯作者：
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影响因子：
13.5
作者：
Huang, Lifeng;Cai, Jie;Xia, Qiang
通讯作者：
Xia, Qiang