癌症相关成纤维细胞 (CAF) 是肿瘤微环境 (TME) 中的主要细胞类型，并且已在各种肿瘤中鉴定出 CAF 亚群。然而，CAF 如何在空间上协调肝脏 TME 内的其他细胞群以促进癌症进展仍不清楚。我们结合了多区域蛋白质组学（6 名患者，24 个样本）、10X Genomics Visium 空间转录组学（11 名患者，25 个样本）和多重成像（92 名患者，264 个样本）破译成纤维细胞表达异质性、功能多样性、空间分布、共定位和相互作用的技术。新鉴定的CAF亚群通过从5例肝癌患者中分离的细胞和体外功能测定进行了验证。我们鉴定了一个肝脏CAF亚群，以COL1A2、COL4A1、COL4A2、CTGF和FSTL1的表达为标志，并将其命名为F5-CAF。 F5-CAF优先位于肿瘤巢内和肿瘤巢周围，并与肝细胞癌（HCC）中干性较高的癌细胞共定位。 92 名患者的多重染色和 371 名患者的大量转录组表明，HCC 中 F5-CAF 的丰度与较差的预后相关。进一步的体外实验表明，从肝癌患者体内分离的F5-CAF可以促进HCC细胞的增殖和干细胞性。我们在肝癌中鉴定出一个CAF亚群F5-CAF，该亚群与癌症干细胞性和不良预后相关。我们的结果提供了 TME 中的 CAF 子集通过支持癌症干细胞的存活来促进肝癌发展的潜在机制。© 2024。作者。

Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear.We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays.We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells.We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.© 2024. The Author(s).