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Integrating single cell- and spatial- resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma 期刊论文

编号：

B25C55AEA75DB1CC251487E1B78E0895
作者：

Chen, Jiayun#^[1,2,3]Lu, Wenmin#^[1]Lou, Yanni(娄彦妮)#^[4]Liu, Jing#^[3]Liao, Xiwen#^[5]Bai, Yunmeng^[2];Cheng, Guangqing^[2];Zhu, Guangzhi^[5];Feng, Ji^[1,6];Liu, Junqi^[5];Liu, Zhaoji^[7];Jia, Liqun(贾立群)*^[4]Zhou, Jing*^[7]Peng, Tao*^[5]Lu, GuoDong*^[1,6]Wang, Jigang*^[1,2,3]
语种：

英文
期刊：

MOLECULAR CANCER ISSN：1476-4598 2026 年 25 卷 1 期 ; JAN 5
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关键词：

Hepatocellular carcinoma Hepatitis B virus <italic>Clonorchis sinensis</italic> Single cell RNA sequencing Spatial transcriptomics Inter-tumoral heterogeneity
摘要：

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver carcinoma with high lethality. Both of hepatitis B virus (HBV) and Clonorchis sinensis (C. sinensis) are critical infectious contributors to HCC development. However, the inter-tumor heterogeneity and tumor microenvironment (TME) of HCC patients with different infectious background remain largely unknown.MethodsWe compiled a cohort of 269 primary HCC patients to assess the clinical impact of C. sinensis and HBV infections on patient prognosis. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST-seq) analyses were performed on tumor and adjacent normal samples from C. sinensis-associated HCC (CP), and double-infection HCC (DP) patients. Additionally, we integrated publicly available scRNA-seq and ST-seq datasets from HBV-associated (HP) patients. Immunofluorescence, immunohistochemistry and in vitro experiments were conducted to validate inter-tumor heterogeneity among the three HCC subtypes.ResultsC. sinensis infection is significantly associated with poorer prognosis in HCC patients. Multi-omics analyses revealed distinct inter-tumor heterogeneity in epithelial, immune, and stromal compartments across different HCC subtypes. Tumor cells in the DP group exhibited more malignant marker expression, higher copy number variation scores, increased activation of p53 pathway, and worse survival outcomes. Compared with other HCC subtypes, the TME in DP samples was enriched with SPP1+ macrophages, exhausted CD8+ T cells and COL1A1+ fibroblasts. In contrast, the CP and HP groups showed higher proportions of M2-like macrophages and ENPP2+ liver vascular endothelial cells, respectively.ConclusionThese findings decipher the cellular signatures and their interactions within the TME, shedding light on the inter-tumoral heterogeneity driven by different infections, and the development of targeted therapies for infectious HCC.
推荐引用方式
GB/T 7714：

Chen Jiayun,Lu Wenmin,Lou Yanni, et al. Integrating single cell- and spatial- resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma [J].MOLECULAR CANCER,2026,25(1).
APA：

Chen Jiayun,Lu Wenmin,Lou Yanni,Liu Jing,&Wang Jigang.(2026).Integrating single cell- and spatial- resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma .MOLECULAR CANCER,25(1).
MLA：

Chen Jiayun, et al. "Integrating single cell- and spatial- resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma" .MOLECULAR CANCER 25,1(2026).
入库时间：

2026/1/14 10:19:12
更新时间：

2026/1/14 10:19:12
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