{
  "abstract": "Background: Cellular senescence and the senescence-associated secretory phenotype (SASP) can alter communication between tumor cells and the surrounding microenvironment, but the extracellular mediators involved in this process remain poorly defined in lung adenocarcinoma (LUAD). Methods: Bulk transcriptomic analysis was used to characterize senescence-related transcriptional alterations and construct a prognostic signature. ANGPTL4 expression was evaluated in public datasets and clinical samples. Single-cell RNA-sequencing analysis was then performed to map senescence-associated gene-set scores across LUAD cell populations and to examine the cell–cell communication. ANGPTL4 depletion and overexpression were used to assess its effects on LUAD-cell proliferation, migration, and SA-β-gal positivity, while a subcutaneous xenograft model was used to examine tumor growth in vivo. Conditioned-medium and indirect co-culture experiments were performed to assess the effects of ANGPTL4-overexpressing LUAD cells on THP-1-derived macrophage inflammatory responses, and MCC950 was used to evaluate the contribution of NLRP3-associated signaling. Results: Senescence-related transcriptional alterations in LUAD were enriched in inflammatory and immune-related pathways. ANGPTL4 was included in a five-gene prognostic model and selected for functional investigation because it encodes a secreted protein. We found that ANGPTL4 protein levels were increased in LUAD tissues. Single-cell analysis showed relatively high senescence-associated gene-set scores in macrophage-enriched populations, together with stronger cell–cell communication in the higher-score group. ANGPTL4 depletion reduced LUAD-cell migration and SA-β-gal positivity, while its overexpression had the opposite effects and resulted in larger xenograft tumors. Conditioned medium and indirect co-culture experiments showed that ANGPTL4-overexpressing LUAD cells induced inflammatory changes in THP-1-derived macrophages, accompanied by increased NLRP3-associated markers and IL-1β secretion. These changes were partly attenuated by MCC950. Conclusions: These findings suggest that ANGPTL4 is associated with tumor cell–macrophage crosstalk in LUAD and may correlate with senescence-related transcriptional signatures, while the specific biological role of ANGPTL4 remains to be further characterized.",
  "abstract_shown": true,
  "affiliations": [
    "Chest Hospital, Tianjin University, Tianjin 300072, China",
    "Tianjin Institute of Cardiovascular Disease, Tianjin Chest Hospital, Tianjin 300222, China",
    "Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300222, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ying Shi",
      "orcid": "0000-0001-6635-5400"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Han Zhang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yuhang Jiang"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Xin Li",
      "orcid": "0000-0003-0669-0359"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Daqiang Sun",
      "orcid": "0009-0000-6602-357X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/14y6zcge8vvh1.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18213571",
  "fulltext_url": null,
  "id": "14y6zcge8vvh1",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/21/3571",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/14y6zcge8vvh1.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:21:21Z",
      "native_id": "10.3390/cancers18213571",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/21/3571"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2072-6694",
      "subfield": "oncology"
    }
  ],
  "title": "Senescence-Related Transcriptomic Analysis and Functional Characterization of ANGPTL4 in Lung Adenocarcinoma",
  "title_text": "Senescence-Related Transcriptomic Analysis and Functional Characterization of ANGPTL4 in Lung Adenocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:01Z",
  "url": "https://research.draconitic.com/paper/14y6zcge8vvh1",
  "venue": "Cancers",
  "versions": []
}