{
  "abstract": "Background: Small cell carcinoma of the cervix (SCCC) is a rare and highly aggressive neuroendocrine malignancy with poor prognosis and limited therapeutic options. Its clinical management is hampered by a poor understanding of the molecular mechanisms underlying its heterogeneity.\n\nPurpose: This study aimed to define the molecular subtypes of SCCC and delineate their distinct genomic, immune and clinical characteristics through an integrated multi-omics analysis.\n\nMethods: RNA-sequencing data from 19 SCCC tumors were subjected to non-negative matrix factorization (NMF) to identify molecular subtypes. Pathway activation and drug sensitivity profiles were inferred using bioinformatics analyses. Whole-genome sequencing, viral capture sequencing, and OncoScan SNP array profiling were used to uncover subtype-specific genomic alterations. Immunohistochemistry on formalin-fixed paraffin-embedded tissues validated key markers and characterized subgroup-related biology. Survival analyses were performed to assess prognostic relevance.\n\nResults: NMF revealed two robust molecular subtypes distinguished by reciprocal expression of SCG3 and YAP1. The SCG3High/YAP1Low subtype exhibited pronounced neuroendocrine differentiation, an immune-desert microenvironment with scarce CD8 + T-cell infiltration, preferential HPV18 integration at chromosome 8q24.21 leading to MYC amplification, and inferior survival outcomes. In contrast, the SCG3Low/YAP1High subtype showed attenuated neuroendocrine features, enrichment of immune-related pathways, higher CD8 + T cell density, and absence of the preferential HPV18 integration pattern. Cross-cancer analyses revealed a conserved neuroendocrine–immune polarization between SCCC and small cell lung cancer (SCLC), suggesting shared subtype-specific therapeutic vulnerabilities.\n\nConclusion: SCCC can be molecularly classified into two distinct subtypes defined by opposing SCG3 and YAP1 expression patterns, each characterized by unique genomic, immunologic, and clinical profiles. This molecular framework provides a basis for subtype-guided precision oncology in SCCC.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08723-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China",
    "Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei China",
    "University of Chinese Academy of Sciences, Beijing, China",
    "Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang China",
    "Desert Research Centre, Cairo, Egypt",
    "Department of Obstetrics and Gynecology, Peking University People’s Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044 China",
    "City University of Hongkong, Hongkong, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Xinran Fan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yao Jia"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiangqin Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mengjia Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Changzheng Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Silu Meng"
    },
    {
      "affs": [
        4
      ],
      "name": "Ahmed H. Ghonaim"
    },
    {
      "affs": [
        5
      ],
      "name": "Bing Xiao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Junlan Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hongqi Dai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ruoqi Ning"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Haiying Sun"
    },
    {
      "affs": [
        6
      ],
      "name": "Shuaicheng Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ding Ma"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shuang Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ex27hjhzbw1a3.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08723-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732930/",
  "id": "ex27hjhzbw1a3",
  "issns": [
    "1479-5876"
  ],
  "landing_url": "https://doi.org/10.1186/s12967-026-08723-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2713|Cervical Cancer and HPV Research"
    ]
  ],
  "openalex": "W7172528857",
  "pdf_url": null,
  "pmcid": "PMC13732930",
  "pmid": "42983745",
  "published": "2026-08-05",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/ex27hjhzbw1a3.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:49Z",
      "native_id": "PMC13732930",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12967-026-08723-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Cervical Cancer and HPV Research",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "SCG3 and YAP1 define molecular subtypes of small cell carcinoma of the cervix with divergent multi-omics features and prognostic outcomes",
  "title_text": "SCG3 and YAP1 define molecular subtypes of small cell carcinoma of the cervix with divergent multi-omics features and prognostic outcomes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:49Z",
  "url": "https://research.draconitic.com/paper/ex27hjhzbw1a3",
  "venue": "Journal of Translational Medicine",
  "versions": []
}