{
  "abstract": "Objective: Pancreatic ductal adenocarcinoma (PDAC) exhibits profound molecular and metabolic heterogeneity associated with distinct phenotypic states. However, the contribution of transcription factor (TF)-driven regulatory programs to metabolic subtype stratification remains poorly understood. This study aims to determine whether TF-based classification can identify prognostically relevant glycolytic and lipogenic PDAC subtypes.\n\nMethods: Bulk transcriptomic data from multiple PDAC cohorts and single-cell RNA sequencing data were integrated to characterize TF-associated metabolic heterogeneity. Metabolic signatures and TFs were quantified using single-sample gene set enrichment analysis (ssGSEA) and AddModule Score (AMS). Differential expression, enrichment analysis, integrative bulk and single-cell transcriptomic analysis, and deep neural network-based metabolic flux modeling were performed to investigate metabolic programs and functional differences between TF-defined subtypes. Additionally, RNA interference, RT-qPCR, lipid droplets staining, lactate assay, and transwell assays were used to evaluate the roles of TP63 in metabolic regulation.\n\nResults: Glycolytic and lipogenic TF-defined metabolic subtypes were identified across multiple independent PDAC cohorts. These subtypes exhibited distinct metabolic programs, differentiation states, and prognostic outcomes. The glycolytic TF-defined subtype was associated with worse prognosis and differentiation, whereas the lipogenic TF-defined subtype exhibited more favorable clinical features. Integration of public bulk and single-cell transcriptomic analyses, together with deep neural network-based metabolic flux modeling, revealed consistent metabolic heterogeneity at both cellular and functional levels. Notably, TP63 was identified as a potential regulator of glycolytic-lipogenic metabolic reprogramming in PDAC.\n\nConclusions: TF-based classification delineates glycolytic and lipogenic subtypes in PDAC, underscoring the critical role of TF-regulated metabolic programs in patient stratification. These findings highlight the prognostic significance of glycolytic and lipogenic metabolic heterogeneity and support the development of metabolism-targeted therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Central Laboratory, Shenzhen Hospital, Beijing University of Chinese Medicine , , ,",
    "Department of Human Cell Biology and Genetics, SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology , , ,",
    "Biotherapy Center, Shenzhen Third People’s Hospital , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jie Ke"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuai Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Junming Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Fenfang Wu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5fefv91yb8tvh.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1900370",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672013/?tool=EBI",
  "id": "5fefv91yb8tvh",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672013",
  "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",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7215028621",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672013/pdf/?tool=EBI",
  "pmcid": "PMC13672013",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5fefv91yb8tvh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13672013",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13672013"
    },
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1900370",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1900370/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "Transcription factor-driven metabolic stratification reveals glycolytic and lipogenic subtypes with distinct prognostic and functional features in pancreatic cancer",
  "title_text": "Transcription factor-driven metabolic stratification reveals glycolytic and lipogenic subtypes with distinct prognostic and functional features in pancreatic cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:13Z",
  "url": "https://research.draconitic.com/paper/5fefv91yb8tvh",
  "venue": "Frontiers in oncology",
  "versions": []
}