{
  "abstract": "Diffuse gastric cancer (DGC) is an aggressive gastric cancer subtype with a poor prognosis. The RHOA Y42C mutation is recurrent in DGC, but its independent oncogenic role is unclear. Next-Generation Sequencing of 431 DGC cases revealed that most RHOA mutations occurred without CDH1 alterations. Using genetically engineered gastric organoids, we show that RhoaY42C, along with KrasG12D and Trp53 loss (RKP), induces DGC, independently of Cdh1 loss. Single-cell and spatial transcriptomics reveal that RKP tumors exhibit mucinous histopathology and a specific lineage trajectory from Aqp5⁺ cells to Muc1/Muc4⁺ cells. RKP tumors create an immunosuppressive tumor microenvironment where AREG, transactivated by RhoA Y42C-YAP1, causes T cell exhaustion via PD-1 upregulation. Unlike E-cadherin loss-associated DGC, RKP tumors are highly susceptible to PD-1 blockade. Additionally, the RHOA Y42C mutation correlates with PD-1 upregulation in human DGC samples. These findings redefine the oncogenic role of RhoA Y42C, confirming its sufficiency for DGC development and suggesting PD-1 inhibition as a viable therapeutic option for DGC patients carrying this mutation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Kyung-Pil Ko",
      "orcid": "0000-0002-9554-5972"
    },
    {
      "name": "Sangmin Kim"
    },
    {
      "name": "Jinho Jang"
    },
    {
      "name": "Yoojeong Seo",
      "orcid": "0000-0001-7243-5386"
    },
    {
      "name": "Gengyi Zou",
      "orcid": "0000-0002-5399-8674"
    },
    {
      "name": "Jie Zhang"
    },
    {
      "name": "Sohee Jun"
    },
    {
      "name": "Brittany Morrow"
    },
    {
      "name": "Jaffer A. Ajani",
      "orcid": "0000-0001-9946-0629"
    },
    {
      "name": "Ryan J. Park"
    },
    {
      "name": "Yuan-Hung Lo",
      "orcid": "0000-0002-9704-3124"
    },
    {
      "name": "Michael A. Curran",
      "orcid": "0000-0003-4996-7207"
    },
    {
      "name": "Kim Hyunki",
      "orcid": "0000-0003-2292-5584"
    },
    {
      "name": "Jae-Il Park",
      "orcid": "0000-0002-0737-2654"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ca9bdkprg2g5.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-78304-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13728165",
  "id": "4ca9bdkprg2g5",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-78304-3",
  "language": "eng",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-78304-3_reference.pdf",
  "pmcid": "PMC13728165",
  "pmid": "42971956",
  "published": "2026-10-06",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/4ca9bdkprg2g5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-78304-3",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-78304-3"
    },
    {
      "first_seen": "2026-11-04T15:20:44Z",
      "native_id": "MED:42971956",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42971956"
    },
    {
      "first_seen": "2026-11-06T12:23:54Z",
      "native_id": "PMC13728165",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41467-026-78304-3"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "RhoA Y42C drives cell plasticity and PD-1-mediated immune evasion of diffuse gastric cancer",
  "title_text": "RhoA Y42C drives cell plasticity and PD-1-mediated immune evasion of diffuse gastric cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:23:54Z",
  "url": "https://research.draconitic.com/paper/4ca9bdkprg2g5",
  "venue": "Nature Communications",
  "versions": []
}