{
  "abstract": "Introduction\n\nVessel encapsulating tumor cluster (VETC) defines a distinct vascular phenotype of hepatocellular carcinoma (HCC), characterized by tumor nests fully encased within a continuous endothelial lining. This architecture correlates with poor prognosis and enhanced sensitivity to anti-angiogenic therapies. To dissect the morphological, phenotypical, molecular, and functional programs that define VETC-associated ECs in HCC and to identify endothelial pathways potentially driving VETC vascular organization and tumor progression.Methods\n\nBiological samples (blood, plasma, Peripheral blood mononuclear cells, and tissue) were collected from VETC+ and VETC- HCCs. Quantitative tissue imaging was integrated with EC-specific molecular profiling. Vascular architecture was assessed on whole-slide images, and purified tumor ECs underwent targeted and transcriptome-wide gene expression analyses.Results\n\nECs from both VETC+ and VETC- HCCs lacked pro-growth and anti-apoptotic features. VETC+ ECs show overexpression of pro-angiogenic and immune-modulatory factors, in particular vascular endothelial growth factor alpha, FGF and IL10, and a specific gene signature involved in metabolic reprogramming, increased trafficking and migratory capacity. VETC+ transcriptional phenotype is driven by a coordinated hepatic xenobiotic-sensing network in which HNF4A and HNF1A provide the dominant regulatory architecture, while NFE2L2 contributes a distinct regulatory layer governing the antioxidant response elements-dependent arm of the xenobiotic and oxidative-stress response.Conclusion\n\nVETC+ ECs actively shape the HCC microenvironment through the release of angiogenic and immunomodulatory cues. These findings support the existence of a specialized angiocrine program in VETC+ HCC.",
  "abstract_shown": true,
  "affiliations": [
    "Pathology Unit, IRCCS Humanitas Research Hospital, Milan, Italy.",
    "Department of Biomedical Sciences, Humanitas University, Milan, Italy.",
    "Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.",
    "Hepatobiliary Immunopathology Lab, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy.",
    "Department of Immunology and Inflammation, IRCCS Humanitas Research Hospital, Rozzano, Italy.",
    "Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy.",
    "Division of Hepatobiliary and General Surgery, Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy.",
    "Hepatobiliary Unit, Department of Minimally Invasive General and Oncologic Surgery, Humanitas Gavazzeni University Hospital, Bergamo, Italy.",
    "Department of Electrical Engineering and Information Technologies, University of Naples \"Federico II\", Naples, Italy."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Barbara Durante"
    },
    {
      "affs": [
        0
      ],
      "name": "Simone Zanella"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesco de Napoli"
    },
    {
      "affs": [
        0
      ],
      "name": "Beatrice Esposito"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Camilla De Carlo"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Reha Akpinar"
    },
    {
      "affs": [
        1
      ],
      "name": "Cristina Richichi"
    },
    {
      "affs": [
        2
      ],
      "name": "Francesca Lazzaroni"
    },
    {
      "affs": [
        3
      ],
      "name": "Barbara Franceschini"
    },
    {
      "affs": [
        3
      ],
      "name": "Cristiana Soldani"
    },
    {
      "affs": [
        4
      ],
      "name": "Fabio Grizzi"
    },
    {
      "affs": [
        4
      ],
      "name": "Fabio Pasqualini"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Ana Lleo"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Guido Torzilli",
      "orcid": "0000-0001-5798-5021"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Fabio Procopio"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Luca Viganò"
    },
    {
      "affs": [
        1
      ],
      "name": "Salvatore Piscuoglio",
      "orcid": "0000-0003-2686-2939"
    },
    {
      "affs": [
        1
      ],
      "name": "Charlotte K Y Ng"
    },
    {
      "affs": [
        1
      ],
      "name": "Federica Airi"
    },
    {
      "affs": [
        1
      ],
      "name": "Elvezia Paraboschi"
    },
    {
      "affs": [
        8
      ],
      "name": "Ines Simeone"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Luca Di Tommaso",
      "orcid": "0000-0002-9013-4728"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bnz4p9cnq64yq.bib",
  "cited_by": 0,
  "doi": "10.1159/lic/admag014",
  "fulltext_url": "https://europepmc.org/articles/PMC13688697",
  "id": "bnz4p9cnq64yq",
  "issns": [
    "2235-1795",
    "1664-5553"
  ],
  "landing_url": "https://europepmc.org/article/MED/42924056",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
  ],
  "openalex": "W7218866388",
  "pdf_url": "https://europepmc.org/articles/PMC13688697?pdf=render",
  "pmcid": "PMC13688697",
  "pmid": "42924056",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bnz4p9cnq64yq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:36Z",
      "native_id": "MED:42924056",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42924056"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Endothelial Cells Contribute to the Immune-Vascular Milieu Characterizing VETC+ HCC.",
  "title_text": "Endothelial Cells Contribute to the Immune-Vascular Milieu Characterizing VETC+ HCC.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:36Z",
  "url": "https://research.draconitic.com/paper/bnz4p9cnq64yq",
  "venue": "Liver cancer",
  "versions": []
}