{
  "abstract": "Background: Ovarian cancer (OC), particularly high-grade serous ovarian carcinoma (HGSOC), remains a lethal gynecological malignancy characterized by frequent recurrence and treatment resistance. Ferroptosis is governed by nutrient-related metabolic processes involving iron handling, cystine–glutathione antioxidant defense, lipid peroxidation, amino-acid metabolism, and cellular energy metabolism. However, the organization of these programs across bulk tumors and individual tumor-microenvironment compartments remains incompletely understood.\n\nMethods: Bulk RNA-sequencing data from The Cancer Genome Atlas ovarian cancer cohort (TCGA-OV) were analyzed in 421 primary tumors, with 419 patients evaluable for overall survival, using a curated 40-gene ferroptosis–nutrient-metabolic panel. Gene correlations, module scores, survival associations, a 10-fold cross-validated LASSO-Cox ferroptosis risk score (FRS), immune-marker enrichment, and immune-checkpoint correlations were evaluated. Single-cell RNA-sequencing data from GSE146026 were analyzed in a 10x cohort of 9,609 cells from 6 patients, with a Smart-seq2 cohort of 1,297 cells used for consistency analyses. Selected genes were further validated by RT-qPCR in hTERT FNE1, NIH:OVCAR-3, and Caov-3 cells.\n\nResults: FTL, RPL8, FTH1, LDHA, and GPX4 showed the highest mean expression in TCGA-OV. Lower SLC7A11 expression was associated with shorter survival (HR = 0.83 per SD, 95% CI 0.73–0.94, p = 0.004), whereas higher LPCAT3 expression was associated with shorter survival (HR = 1.19, p = 0.010), although neither survived false-discovery-rate correction. The two-gene FRS separated survival groups (log-rank p = 0.019) but showed modest discrimination (C-index = 0.56; held-out concordance = 0.55). The ferroptosis–nutrition score correlated most strongly with macrophage marker enrichment (rho = 0.46). At single-cell resolution, the overall score was highest in fibroblasts, epithelial tumor cells, and macrophages, whereas the iron-storage module was highest in macrophages. Cross-platform concordance was observed between 10x and Smart-seq2 (rho = 0.63) and between epithelial pseudobulk and TCGA-OV bulk expression (rho = 0.65). RT-qPCR confirmed higher expression of FTL, FTH1, GPX4, SLC7A11, and LPCAT3 in both ovarian-cancer cell lines than in hTERT FNE1.\n\nConclusion: Ferroptosis-related nutrient-metabolic genes display coordinated but cell-type-specific organization in ovarian cancer and are linked to immune-marker enrichment. RT-qPCR provides orthogonal expression-level validation of selected candidates. The FRS remains exploratory, and the transcriptomic scores should not be interpreted as direct measures of ferroptotic activity or clinical nutritional status.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Reproductive Medicine, Qingdao Municipal Hospital , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yan Xing"
    },
    {
      "affs": [
        0
      ],
      "name": "Lulu Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenjuan Ling"
    },
    {
      "affs": [
        0
      ],
      "name": "Lingling Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5a7crw52n62ck.bib",
  "cited_by": 0,
  "doi": "10.3389/fpubh.2026.1967476",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672651/?tool=EBI",
  "id": "5a7crw52n62ck",
  "issns": [
    "2296-2565"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672651",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7215807530",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672651/pdf/?tool=EBI",
  "pmcid": "PMC13672651",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5a7crw52n62ck.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13672651",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13672651"
    },
    {
      "first_seen": "2026-10-30T12:20:22Z",
      "native_id": "10.3389/fpubh.2026.1967476",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpubh.2026.1967476/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2296-2565",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Ferroptosis and nutrient-metabolic pathway genes in ovarian cancer: integrated bulk and single-cell analysis of Iron-metabolic programs, immune-marker enrichment, and prognosis",
  "title_text": "Ferroptosis and nutrient-metabolic pathway genes in ovarian cancer: integrated bulk and single-cell analysis of Iron-metabolic programs, immune-marker enrichment, and prognosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:22Z",
  "url": "https://research.draconitic.com/paper/5a7crw52n62ck",
  "venue": "Frontiers in public health",
  "versions": []
}