{
  "abstract": "Background/objectives\n\nColorectal cancer (CRC) is among the most diagnosed malignancies and is a leading cause of cancer-related deaths globally. Beyond canonical CRC driver mutations, additional molecular alterations such as dysregulated gene expression and epigenetic reprogramming shape the disease behavior and may represent potential candidate biomarkers. The Four and a Half LIM domain (FHL) family, specifically FHL1, has been implicated as a tumor suppressor in CRC epithelial cells. However, FHL1 expression is reduced in CRC and whether this reduction in heterogenous tumors is cell type-specific remains unknown.Methods\n\nIn this study, we integrated bulk genomic, transcriptomic and survival data from the cancer genome atlas (TCGA) with publicly available single-cell transcriptomic and epigenomic datasets to identify where and how FHL1 expression is dysregulated in CRC.Results\n\nWhile somatic mutations of FHL family genes are infrequent and non-recurrent, downregulation of FHL1 in CRC tissue is evident and shows a modest association with longer survival that is not independent of clinical factors. Notably, single-cell analysis across three independent studies revealed that FHL1 expression is largely restricted to fibroblasts and is specifically downregulated in cancer-associated fibroblasts (CAFs). FHL1 expression is inversely associated with activated CAF markers FAP and ACTA2, while normal fibroblast markers WNT2B and RSPO3 demonstrate a similar expression pattern to FHL1. Finally, chromatin accessibility at the FHL1 promoter was substantially reduced in CAFs relative to pre-CAFs and normal fibroblasts.Conclusions\n\nOur study identifies that FHL1 downregulation is specific to CAFs in CRC and is accompanied by chromatin inaccessibility within the FHL1 promoter in CAFs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia.",
    "Laboratory Genetics Specialist, Forensic Medical Services Center, Ministry of Health, Riyadh 13211, Saudi Arabia.",
    "Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Border University, Arar 91431, Saudi Arabia.",
    "Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia.",
    "Department of Anatomic Pathology, Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh 11211, Saudi Arabia.",
    "Pathology Department, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Abdullah A Alqasem"
    },
    {
      "affs": [
        0
      ],
      "name": "Waad Al-Burayk"
    },
    {
      "affs": [
        0
      ],
      "name": "Muneira Habjar"
    },
    {
      "affs": [
        0
      ],
      "name": "Batla Aldawsari"
    },
    {
      "affs": [
        0
      ],
      "name": "Alanoud Almansour"
    },
    {
      "affs": [
        1
      ],
      "name": "Mohammad A Alahmari",
      "orcid": "0009-0000-3392-5454"
    },
    {
      "affs": [
        0
      ],
      "name": "Adel M Alqarni"
    },
    {
      "affs": [
        0
      ],
      "name": "Helal G Alanazi",
      "orcid": "0009-0004-3843-1137"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Mohammed M Alruwaili",
      "orcid": "0000-0003-2811-4387"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Emad Alqassim",
      "orcid": "0009-0004-7070-1993"
    },
    {
      "affs": [
        0
      ],
      "name": "Ahmed Rokan",
      "orcid": "0000-0003-0140-9353"
    },
    {
      "affs": [
        0
      ],
      "name": "Abdulrahman A Alahmari",
      "orcid": "0000-0002-7211-3739"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7bq7akzw48sx3.bib",
  "cited_by": 0,
  "doi": "10.3390/genes17101210",
  "fulltext_url": "https://europepmc.org/articles/PMC13704643",
  "id": "7bq7akzw48sx3",
  "issns": [
    "2073-4425"
  ],
  "landing_url": "https://europepmc.org/article/MED/42938326",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Cells and Metastasis"
    ]
  ],
  "openalex": "W7214746555",
  "pdf_url": "https://europepmc.org/articles/PMC13704643?pdf=render",
  "pmcid": "PMC13704643",
  "pmid": "42938326",
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7bq7akzw48sx3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:24Z",
      "native_id": "MED:42938326",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42938326"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Cells and Metastasis",
      "subfield": "oncology"
    }
  ],
  "title": "FHL1 Downregulation Is Specific to Cancer-Associated Fibroblasts and Linked to Reduced Chromatin Accessibility in Colorectal Cancer.",
  "title_text": "FHL1 Downregulation Is Specific to Cancer-Associated Fibroblasts and Linked to Reduced Chromatin Accessibility in Colorectal Cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:24Z",
  "url": "https://research.draconitic.com/paper/7bq7akzw48sx3",
  "venue": "Genes",
  "versions": []
}