{
  "abstract": "Background\n\nPulmonary metastasis/relapse (PM/R) is a major cause of osteosarcoma treatment failure. We aimed to develop a compact transcriptomic PM/R risk score and characterize associated immune and single-cell programs.Methods\n\nTARGET-OS bulk RNA-seq was used for discovery and GSE21257 for external validation. Differential expression, multi-algorithm feature selection and LASSO regression were used to construct the score. Clinical associations were assessed by PM/R classification, survival and calibration analyses. Immune signature scoring, weighted gene co-expression network analysis (WGCNA), single-cell projection, in silico virtual HERC5 knockout, PROGENy/DoRothEA, CellChat and exploratory drug-reversal analyses were used for biological interpretation.Results\n\nA 9-gene score comprising HERC5, GPR141, SLC45A4, LCN15, MXI1, UCK2, KRTAP13-2, KCNK6 and TRABD2A showed high apparent discrimination in TARGET-OS (AUC = 0.922). A reduced seven-gene GSE21257 implementation achieved an AUC of 0.728. High-risk tumors were enriched for PM/R and had poorer event-free survival (HR = 3.14, 95% CI, 1.60-6.16) and overall survival (HR = 3.75, 95% CI, 1.60-8.79). High-risk disease showed reduced antigen-presentation, IFN-gamma, T-cell, CD8 T-cell, NK-cell and cytotoxicity signatures. WGCNA identified a protective immune module, while single-cell and in silico virtual-knockout analyses prioritized HERC5 as a candidate immune-associated node linked to antigen-presentation genes. Regulatory and communication analyses suggested reduced JAK-STAT/IRF activity and SPP1/MIF-centered microenvironmental signaling.Conclusions\n\nThis study defines a PM/R-focused transcriptomic risk score and links high-risk osteosarcoma to immune attenuation and a HERC5-associated antigen-presentation program, providing a framework for future validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.",
    "Department of Orthopedics, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China. Electronic address: zlyygk@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhangfu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Baicheng Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiqing Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shengji Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5kdbwaptvbsfy.bib",
  "cited_by": 0,
  "doi": "10.1016/j.tranon.2026.103070",
  "fulltext_url": "https://europepmc.org/articles/PMC13677953",
  "id": "5kdbwaptvbsfy",
  "issns": [
    "1936-5233"
  ],
  "landing_url": "https://europepmc.org/article/MED/42858644",
  "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",
      "2740|Sarcoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7221342799",
  "pdf_url": "https://europepmc.org/articles/PMC13677953?pdf=render",
  "pmcid": "PMC13677953",
  "pmid": "42858644",
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5kdbwaptvbsfy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42858644",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42858644"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Sarcoma Diagnosis and Treatment",
      "subfield": "general"
    }
  ],
  "title": "Integrative bulk and single-cell transcriptomics identifies a HERC5-linked immune-attenuated risk program for pulmonary metastasis/relapse in osteosarcoma.",
  "title_text": "Integrative bulk and single-cell transcriptomics identifies a HERC5-linked immune-attenuated risk program for pulmonary metastasis/relapse in osteosarcoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/5kdbwaptvbsfy",
  "venue": "Translational oncology",
  "versions": []
}