{
  "abstract": "ObjectiveOsteosarcoma prognosis remains challenging, and reliable molecular determinants are lacking. We integrated multi-dimensional functional genomic and transcriptomic data to construct a prognostic model and investigated the key candidate gene CCT3 in osteosarcoma malignancy.MethodsWe intersected CRISPR-Cas9 dependency genes with differentially expressed genes to derive a 64-gene candidate pool, followed by stepwise Cox regression to build a risk model. Model performance was validated in training and external cohorts. Immune microenvironment, drug sensitivity, and experimental validation were performed following CCT3 knockdown.ResultsAn 8-gene risk model was constructed and significantly stratified overall survival. The high-risk group showed lower immune scores, reduced immune-cell infiltration, and downregulation of multiple immune checkpoint genes, indicating an immune-poor phenotype. Among 7 drugs with differential sensitivity, the high-risk group was more sensitive to 6 agents, including AZ6102, while showing resistance to Entospletinib. CCT3 was overexpressed in osteosarcoma tissues and cell lines; its knockdown suppressed proliferation and clonogenicity. Mechanistically, CCT3 depletion attenuated Wnt/beta-catenin signaling and reduced stemness markers CD24 and c-MYC.ConclusionOur integrative approach establishes an effective prognostic model for osteosarcoma and identifies CCT3 as a pro-tumorigenic gene, likely through the beta-catenin/c-MYC axis, representing a promising prognostic biomarker and therapeutic vulnerability.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "Jiangbao Xu"
    },
    {
      "name": "Shengkun Hong"
    },
    {
      "name": "Zhuo Zhang"
    },
    {
      "name": "Wei Wang"
    },
    {
      "name": "Ankai Xu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aamhdpngjercv.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1978392",
  "fulltext_url": null,
  "id": "aamhdpngjercv",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978392",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-11",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/aamhdpngjercv.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:21:03Z",
      "native_id": "10.3389/fimmu.2026.1978392",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978392"
    },
    {
      "first_seen": "2026-11-11T12:24:56Z",
      "native_id": "10.3389/fimmu.2026.1978392",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1978392/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Integrative functional-genomics analysis identifies CCT3 as a prognostic biomarker in osteosarcoma, involving the beta-catenin/c-MYC axis in malignant progression",
  "title_text": "Integrative functional-genomics analysis identifies CCT3 as a prognostic biomarker in osteosarcoma, involving the beta-catenin/c-MYC axis in malignant progression",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T00:21:19Z",
  "url": "https://research.draconitic.com/paper/aamhdpngjercv",
  "venue": "Frontiers in Immunology",
  "versions": []
}