{
  "abstract": "Objective\n\nColorectal cancer (CRC) is molecularly, cellularly and spatially heterogeneous, and current staging systems and biomarkers incompletely explain prognosis and treatment response. This study integrated transcriptomics, machine learning, single-cell RNA sequencing, spatial transcriptomics and in vitro experiments to prioritize candidate CRC-associated markers and characterize their potential biological and clinical relevance.Methods\n\nGSE44861 and GSE44076 from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) were used for differential expression, consensus differentially expressed gene (DEG) identification and functional enrichment analyses. Four machine-learning algorithms were applied for feature selection. Candidate genes were prioritized by differential expression, model importance and receiver operating characteristic (ROC) performance. GSE231559 single-cell data and spatial transcriptomics characterized the cellular source, pseudotime dynamics and spatial distribution of the core gene. TCGA-COAD assessed prognosis, pathways and computationally predicted drug sensitivity. Western blotting, Transwell and MTT assays were used for experimental validation, and public immunohistochemistry images from the Human Protein Atlas were used as supplementary protein-expression evidence.Results\n\nWe identified 544 consensus DEGs enriched in leukocyte migration, chemotaxis, extracellular matrix organization, cytokine activity and metabolic pathways. Six genes were jointly selected: CLDN1, CDH3, KRT24, MMP7, NEBL and SCGN. CLDN1 was markedly upregulated and showed the highest tumour-versus-normal discrimination among the six candidates in the TCGA-COAD cohort. Single-cell and spatial analyses showed that CLDN1 was mainly expressed in CRC epithelial cells, displayed increasing expression across the inferred pseudotime ordering, and was enriched in malignant and mixed regions. In the TCGA-COAD cohort, high CLDN1 expression was associated with poorer overall survival and pathways involving the cell cycle, proteasome, autophagy, Hippo, ErbB and CRC. CLDN1 manipulation altered CRC-cell invasion and in vitro response to Nutlin-3a (-).Conclusion\n\nThese findings support CLDN1 as a candidate CRC-associated marker linked to malignant epithelial-cell states, tumour-associated spatial heterogeneity, invasive phenotype and Nutlin-3a (-) response. Further independent and prospective validation is required to determine its clinical diagnostic, prognostic and treatment-response relevance.",
  "abstract_shown": true,
  "affiliations": [
    "The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China.",
    "Department of Oncology, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China.",
    "Translational Medicine Research Center, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China.",
    "Scientific Research Management Office, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China.",
    "Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.",
    "Department of Microbiology and Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China. Electronic address: lnj717@zzu.edu.cn.",
    "Translational Medicine Research Center, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China. Electronic address: haozhe@hactcm.edu.cn.",
    "Translational Medicine Research Center, The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, Henan, China. Electronic address: zhaorui1126@hactcm.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenqi Shan"
    },
    {
      "affs": [
        0
      ],
      "name": "Qianyu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Wei Yuan"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruiting Feng"
    },
    {
      "affs": [
        3
      ],
      "name": "Peiyao Hu"
    },
    {
      "affs": [
        4
      ],
      "name": "Zongmian Song"
    },
    {
      "affs": [
        2
      ],
      "name": "Yanfeng Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Chenghan Luo"
    },
    {
      "affs": [
        5
      ],
      "name": "Ningjing Lei"
    },
    {
      "affs": [
        6
      ],
      "name": "Haozhe Zhang"
    },
    {
      "affs": [
        7
      ],
      "name": "Zhaorui Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/espr9jprggant.bib",
  "cited_by": 0,
  "doi": "10.1016/j.tranon.2026.103078",
  "fulltext_url": "https://europepmc.org/articles/PMC13685891",
  "id": "espr9jprggant",
  "issns": [
    "1936-5233"
  ],
  "landing_url": "https://europepmc.org/article/MED/42868715",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Mechanisms of cancer metastasis"
    ]
  ],
  "openalex": "W7221660374",
  "pdf_url": "https://europepmc.org/articles/PMC13685891?pdf=render",
  "pmcid": "PMC13685891",
  "pmid": "42868715",
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/espr9jprggant.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42868715",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42868715"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Mechanisms of cancer metastasis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Machine learning and multi-omics analyses reveal CLDN1 as a candidate marker associated with colorectal cancer invasion and nutlin-3a (-) response.",
  "title_text": "Machine learning and multi-omics analyses reveal CLDN1 as a candidate marker associated with colorectal cancer invasion and nutlin-3a (-) response.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/espr9jprggant",
  "venue": "Translational oncology",
  "versions": []
}