ArticleCell research2023
An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte-tumor cell crosstalk, local immunosuppression and tumor progression.
Article in Cell research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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165 citing papers in PubMed.
- Neoplastic CD3⁺ B cells remodel the DLBCL tumor microenvironment via single-cell and spatial transcriptomics.Cancer biology & therapy · 2026Article
- Unveiling the role of spatial transcriptomics in the analysis of the tumor immune microenvironment (Review).International journal of molecular medicine · 2026Review
- Unraveling the tapestry: Lessons from multi-omics and spatial biology in hepatocellular cancer.Hepatology (Baltimore, Md.) · 2026Review
- Senescent-Like Neutrophils Shape Angiogenic Immunosuppressive Niches in Colorectal Cancer Liver Metastasis.Cancer discovery · 2026Article
- A High-Resolution Stereo-Seq Spatial Transcriptomic Resource for Adult Holstein Cattle Liver.International journal of molecular sciences · 2026Article
- Spatial omics illuminates tumor heterogeneity.Cell reports methods · 2026Review
- N-Acetyltransferase 10 (NAT10) at the crossroads of metabolism, immunology, and cancer biology.Cancer metastasis reviews · 2026Review
- Spatially organized regulated cell death-immune coupling in solid tumors: integrating spatial omics with actionable regulated cell death biology.Molecular cancer · 2026Review
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
- NicheTrans: spatial-aware cross-omics translation.Nature methods · 2026Article
- Integrated LiP-MS and quantitative proteomics reveal coordinated alterations in protein conformation and expression across tumor and peritumoral regions in hepatocellular carcinoma.Scientific reports · 2026Article
- Spatial transcriptomics differences of histopathological growth patterns in colorectal cancer liver metastases.British journal of cancer · 2026Article
- Deciphering the Leading-Edge Spatiotemporal Microenvironment of Hepatocellular Carcinoma for Targeted Drug Discovery Using SpaPred.International journal of molecular sciences · 2026Article
- The PLAU-ITGB1-TGF-β axis orchestrates spatiotemporal reprogramming of fibroblasts at the invasive front to drive dual immunosuppressive niche and immunotherapy resistance in oral squamous cell carcinoma.Cell death & disease · 2026Article
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Reprogramming of valine metabolism mediated by abnormally low ALDH6A1 expression promotes invasive metastasis of gastric cancer.Science advances · 2026Article
- Review
- Tumor microenvironment-specific nanomedicine: from biology-driven to multi-omics-guided precision engineering.Journal of hematology & oncology · 2026Review
- Emerging role of proteomics in advancing diagnosis, prognosis, and treatment of liver cancer.Liver research (Beijing, China) · 2026Review
- Accurate, scalable and cross-platform cell identification for high-resolution spatial transcriptomics.Nature genetics · 2026Article
105 more citing papers are in PubMed but not listed here.
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53 authors.
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Abstract
Dissecting and understanding the cancer ecosystem, especially that around the tumor margins, which have strong implications for tumor cell infiltration and invasion, are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments. Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified a 500 µm-wide zone centered around the tumor border in patients with liver cancer, referred to as "the invasive zone". We detected strong immunosuppression, metabolic reprogramming, and severely damaged hepatocytes in this zone. We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2 (referred to collectively as SAAs) located close to the border on the paratumor side. Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes, which subsequently caused SAAs' overexpression in these hepatocytes. Furthermore, overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization, further promoting local immunosuppression, potentially resulting in tumor progression. Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer (n = 423) showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis. Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth. The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis, but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors.
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