{
  "abstract": "High-grade serous ovarian cancer (HGSOC) exhibits substantial molecular heterogeneity during disease progression. We investigated stage-specific changes in PI3K-AKT-associated signaling programs from early tumorigenesis to metastatic disease. Two publicly available microarray datasets, GSE36668 (normal, borderline, and carcinoma; n = 4 per group) and GSE73064 (primary tumor, ascites, and metastasis; n = 5 per group), were analyzed using differential expression, gene set enrichment, protein-protein interaction network analysis, and hub-gene identification. PI3K-AKT-associated genes were subsequently characterized by functional enrichment, exploratory survival analysis using KM Plotter, and independent stage-stratified validation in TCGA-OV. Survival analyses were considered exploratory because KM Plotter-derived p-values were not adjusted for multiple testing. Carcinoma-associated genes were predominantly linked to extracellular matrix remodeling and receptor tyrosine kinase-mediated PI3K signaling. Ascites-associated genes were enriched in integrin-dependent signaling and microenvironmental adaptation, whereas metastasis-associated genes formed inflammatory and survival-related modules involving IL6, JAK1, PTK2, AREG, EIF4E, and HSP90B1. In stage-stratified TCGA-OV analysis, all seven metastasis-associated genes were significantly associated with overall survival in Stage IV disease, supporting the prognostic relevance of the metastatic module. HGSOC progression is characterized by stage-associated reorganization of PI3K-AKT-related signaling rather than uniform pathway activation. The identified molecular programs suggest a transition from RTK-associated proliferative signaling in carcinoma to integrin-dependent survival adaptation in ascites and inflammatory survival signaling during metastasis.",
  "abstract_shown": true,
  "affiliations": [
    "Obstetrics and Gynecology Department, Akre Obstetrics and Gynecology Hospital, Duhok General Directorate of Health, Ministry of Health, Duhok 42001, Kurdistan Region, Iraq.",
    "Department of Gynecology and Obstetrics, Faculty of General Medicine, Koya University, Koya 44023, Kurdistan Region, Iraq.",
    "Department of Stem Cells and Cancer, College of Biotechnology, Amol University of Special Modern Technologies, Amol 49767, Iran.",
    "Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Iman Jaafar Abdulrahman"
    },
    {
      "affs": [
        1
      ],
      "name": "Sana Ismael Ameen"
    },
    {
      "affs": [
        2
      ],
      "name": "Hossein Azizi",
      "orcid": "0000-0001-8246-595X"
    },
    {
      "affs": [
        3
      ],
      "name": "Thomas Skutella",
      "orcid": "0000-0003-4813-1213"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/efp6a4mkky07x.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198700",
  "fulltext_url": "https://europepmc.org/articles/PMC13665355",
  "id": "efp6a4mkky07x",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883944",
  "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",
      "2743|Ovarian cancer diagnosis and treatment"
    ]
  ],
  "openalex": "W7214757806",
  "pdf_url": "https://europepmc.org/articles/PMC13665355?pdf=render",
  "pmcid": "PMC13665355",
  "pmid": "42883944",
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/efp6a4mkky07x.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883944",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883944"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2743|Ovarian cancer diagnosis and treatment",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Stage-Specific Rewiring of PI3K-AKT Signaling During Serous Ovarian Cancer Progression: An Integrated Transcriptomic and Network Analysis.",
  "title_text": "Stage-Specific Rewiring of PI3K-AKT Signaling During Serous Ovarian Cancer Progression: An Integrated Transcriptomic and Network Analysis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/efp6a4mkky07x",
  "venue": "International journal of molecular sciences",
  "versions": []
}