{
  "abstract": "Background\n\nTissue biomarkers may improve risk stratification in locally advanced cervical cancer before definitive concurrent chemoradiotherapy (CCRT). We evaluated pretreatment expression of chromobox 4 (CBX4), NADPH oxidase 4 (NOX4), specificity protein 1 (SP1), and copper transporter 1 (CTR1) in relation to CCRT response and overall survival.Methods\n\nIn this retrospective 1:1 matched case-control study, pretreatment biopsies from 40 patients with locally advanced cervical squamous cell carcinoma (20 CCRT-resistant, 20 CCRT-sensitive) were quantified by AI-assisted digital pathology using H-scores. A parsimonious CBX4 + NOX4 logistic model was evaluated by apparent ROC, leave-one-out cross-validation (LOOCV), repeated stratified 5-fold cross-validation, and bootstrap optimism correction. Overall survival analyses were exploratory.Results\n\nCBX4 and NOX4 expression was lower in CCRT-resistant tumors (median H-score: CBX4, 40.47 vs. 79.62; NOX4, 7.00 vs. 53.93; both p < 0.001), whereas SP1 and CTR1 did not differ. Apparent AUCs were 0.840 for CBX4 and 0.843 for NOX4. The two-marker model had an apparent AUC of 0.903, LOOCV AUC 0.845, repeated 5-fold CV AUC 0.854 ± 0.022, and bootstrap-corrected AUC 0.883. High CBX4 and NOX4 expression was associated with better 5-year overall survival; in joint Cox models, hazard ratios per 1-SD increase were 0.31 (95% CI 0.13-0.74) for CBX4 and 0.48 (0.26-0.90) for NOX4. No histochemically detectable copper deposits were observed.Conclusions\n\nLower pretreatment CBX4 and NOX4 expression was associated with a CCRT-resistant phenotype and poorer overall survival in this small, response-enriched cohort. Internal resampling suggested discrimination, but same-dataset marker selection may introduce residual optimism and does not establish generalizability. Independent validation in a consecutively recruited cohort is required before clinical application. No mechanisms involving DNA repair, ROS, or chemoradiotherapy sensitivity were established.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xianfang Pang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiyun Qin"
    },
    {
      "affs": [
        0
      ],
      "name": "Lilin Que"
    },
    {
      "affs": [
        0
      ],
      "name": "Weiye Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zixuan Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Weili Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiao Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yong Zhang",
      "orcid": "0000-0002-4853-6184"
    },
    {
      "affs": [
        0
      ],
      "name": "Shanshan Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Linjiang Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Fang Wu",
      "orcid": "0009-0002-7749-1525"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/54txk3pccqdkf.bib",
  "cited_by": 0,
  "doi": "10.1002/cam4.72402",
  "fulltext_url": "https://europepmc.org/articles/PMC13680544",
  "id": "54txk3pccqdkf",
  "issns": [
    "2045-7634"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897395",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2729|Endometrial and Cervical Cancer Treatments"
    ]
  ],
  "openalex": "W7222965525",
  "pdf_url": "https://europepmc.org/articles/PMC13680544?pdf=render",
  "pmcid": "PMC13680544",
  "pmid": "42897395",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/54txk3pccqdkf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42897395",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897395"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Endometrial and Cervical Cancer Treatments",
      "subfield": "reproductive-child"
    }
  ],
  "title": "CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.",
  "title_text": "CBX4 and NOX4 Expression Are Associated With Chemoradiotherapy Response and Overall Survival in Locally Advanced Cervical Squamous Cell Carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/54txk3pccqdkf",
  "venue": "Cancer medicine",
  "versions": []
}