{
  "abstract": "Background\n\nEntosis is an actomyosin-dependent cell-in-cell process that may culminate in lysosome-mediated entotic cell death and is implicated in tumor evolution. Its clinical relevance in lung adenocarcinoma (LUAD) remains unclear.Methods\n\nTo construct an Entosis-related Prognostic Prediction Index (EPPI), this study integrated TCGA-LUAD transcriptomic, clinical, and somatic mutation data. Three independent GEO cohorts provided external validation. The initial candidate gene set covered components driving cell-in-cell formation and the intracellular degradation of internalized cells. For subgroup comparison, the analytical approach incorporated survival analysis, functional enrichment, tumor microenvironment profiling, mutation analysis, immunotherapy assessment, and drug-sensitivity prediction. Tissue and cellular distributions of the EPPI genes were mapped using spatial transcriptomics and single-cell RNA sequencing. Molecular docking assessed predicted drug-target interactions. Finally, in vitro RAC1 knockdown experiments evaluated the cellular function of a representative EPPI gene.Results\n\nComprising RND3, RAC1, KRAS, CTNNA1, AURKA, and ACTB, the final EPPI consistently stratified overall survival across all cohorts and showed moderate prognostic discrimination. The high-EPPI group had greater tumor purity and mutational burden, with enhanced cell-cycle, DNA-repair, epithelial-mesenchymal transition, and NF-κB programs, whereas the low-EPPI group showed greater immune and stromal infiltration. TIDE and immunophenoscores also differed between subgroups. Drug-response models predicted greater sensitivity to cisplatin and paclitaxel in the high-EPPI group and to several targeted agents in the low-EPPI group. Molecular docking predicted RAC1-EHT-1864 and AURKA-alisertib interactions. Spatial and single-cell analyses showed heterogeneous EPPI-gene expression, with ACTB and RAC1 broadly distributed and AURKA restricted to selected populations. RAC1 depletion suppressed LUAD-cell proliferation, DNA synthesis, migration, and invasion.Conclusion\n\nThe EPPI is an entosis-informed prognostic index for survival stratification in LUAD. Based on this index, patients can be separated into subgroups with distinct proliferative features, genomic alterations, tissue compositions, and predicted drug sensitivities. These findings associate entosis-related molecular features with distinct cellular and clinical characteristics of LUAD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Traditional Chinese Medicine Preventive Healthcare, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.",
    "Department of Thoracic Surgery, Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China.",
    "Institute of Respiratory Diseases, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.",
    "The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, China.",
    "Department of Internal Medicine of Oncology and Hematology, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.",
    "Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yinqin Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Wen Zhao"
    },
    {
      "affs": [
        2
      ],
      "name": "Shuyi Mu"
    },
    {
      "affs": [
        3
      ],
      "name": "Silun Liang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yanping Wen"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaobin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Chengyan Zhan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanqi Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Ling Tang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuqin Wu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ziyou Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Hong Fang"
    },
    {
      "affs": [
        4
      ],
      "name": "Yubin Ding"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1r8mgrb7qzfjj.bib",
  "cited_by": 0,
  "doi": "10.3389/fcell.2026.1943127",
  "fulltext_url": "https://europepmc.org/articles/PMC13677699",
  "id": "1r8mgrb7qzfjj",
  "issns": [
    "2296-634X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42898290",
  "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": "W7220432788",
  "pdf_url": "https://europepmc.org/articles/PMC13677699?pdf=render",
  "pmcid": "PMC13677699",
  "pmid": "42898290",
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1r8mgrb7qzfjj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898290",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898290"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Ferroptosis and cancer prognosis",
      "subfield": "general"
    }
  ],
  "title": "An entosis-informed prognostic index for survival stratification and molecular characterization in lung adenocarcinoma.",
  "title_text": "An entosis-informed prognostic index for survival stratification and molecular characterization in lung adenocarcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/1r8mgrb7qzfjj",
  "venue": "Frontiers in cell and developmental biology",
  "versions": []
}