ArticleMolecular cancer2026
Integrating single cell- and spatial- resolved transcriptomics unravels the inter-tumor heterogeneity and immunosuppressive landscape in HBV- and Clonorchis sinensis-associated hepatocellular carcinoma.
Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Disulfidptosis: Mechanisms, evidence boundaries, and translational opportunities.Redox biology · 2026Review
- Review
- Chronic hepatitis B and perioperative chemotherapy efficacy in colorectal liver metastases: an exploratory analysis of clinical and mechanistic evidence.Frontiers in immunology · 2026Article
- IntegratingFrontiers in immunology · 2026Review
- Functional Interpretation of Recurrent Genetic Variants in Hepatocellular Carcinoma: Molecular Consequences and Clinical Relevance.Human mutation · 2026Review
- The MAPK Pathway Coordinates an Immunosuppressive Microenvironment in Colorectal Cancer: A Single-Cell Guided Prognostic Model.Cancer informatics · 2026Article
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16 authors.
Funding
Abstract
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
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.
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