{
  "abstract": "ObjectiveDiffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy, and the clinical significance of PD-L1 expression has not yet been fully elucidated. This study aims to analyze the molecular differences between PD-L1-positive and PD-L1-negative DLBCL using omics approaches and to explore their potential regulatory mechanisms.MethodsPD-L1 expression was assessed by immunohistochemistry in 72 cases of DLBCL and 12 cases of reactive hyperplasia (RH) lymph nodes as controls, followed by survival analysis. Three representative samples were selected from each of the PD-L1-positive DLBCL, PD-L1-negative DLBCL, and RH groups for data-independent acquisition (DIA) quantitative proteomics and phosphoproteomics analysis. Bioinformatics analyses included GO/KEGG enrichment analysis, PPI network construction, kinase-substrate enrichment analysis (KSEA), and motif analysis. Key findings were further validated in DLBCL cell lines via qRT-PCR and Western blotting, and functionally validated through CARD11 knockdown and PS-1145-mediated IKBKB inhibition.ResultsThe PD-L1 positivity rate in DLBCL was 69.4%; PD-L1 positivity was significantly associated with poorer overall survival. Integrated proteomics and phosphoproteomics analyses revealed that, compared with PD-L1-negative DLBCL, CARD11 was the only protein in PD-L1-positive DLBCL that was upregulated at both the protein abundance and phosphorylation levels. KSEA and kinase-substrate network analyses predicted significant differences in IKBKB expression between PD-L1-positive and PD-L1-negative groups and identified CARD11 S515 as a potential downstream phosphorylation site of IKBKB. GSEA further indicated that the NF-κB signaling pathway was significantly enriched in Group A at both the protein and phosphorylation levels. In vitro validation confirmed that IKBKB, phosphorylated CARD11, phosphorylated P65, and PD-L1 were simultaneously upregulated in DLBCL cells; furthermore, knocking down CARD11 or inhibiting IKBKB reduced NF-κB pathway activity and PD-L1 expression.ConclusionThese findings suggest that the IKBKB–CARD11–NF-κB–PD-L1 regulatory axis may be involved in immune evasion and poor prognosis in PD-L1-positive DLBCL. This regulatory axis provides omics evidence for PD-L1-based prognostic stratification and potential targeted combination immunotherapy strategies.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "name": "Yueyue Chen"
    },
    {
      "name": "Bo Gao"
    },
    {
      "name": "Yun Pan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bab99d7tkn51v.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1922036",
  "fulltext_url": null,
  "id": "bab99d7tkn51v",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1922036",
  "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": [
    [
      "feed-journal",
      "medicine/oncology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bab99d7tkn51v.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T06:20:10Z",
      "native_id": "10.3389/fonc.2026.1922036",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1922036"
    },
    {
      "first_seen": "2026-11-09T12:23:35Z",
      "native_id": "10.3389/fonc.2026.1922036",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1922036/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Proteomics and phosphoproteomics analysis of diffuse large B-cell lymphoma based on PD-L1 expression subtyping",
  "title_text": "Proteomics and phosphoproteomics analysis of diffuse large B-cell lymphoma based on PD-L1 expression subtyping",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:42Z",
  "url": "https://research.draconitic.com/paper/bab99d7tkn51v",
  "venue": "Frontiers in Oncology",
  "versions": []
}