{
  "abstract": "Background: Immune checkpoint inhibitors (ICIs) have transformed the management of advanced non-small cell lung cancer (NSCLC), but their use is associated with potentially serious immune-related cardiotoxicity, often reflected by elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Identifying patients at risk before treatment initiation remains a major clinical challenge. The aim of this study was to investigate whether peripheral blood transcriptomic profiles are associated with susceptibility to an ICI-related cardiac biomarker-defined phenotype.\n\nMethods: Peripheral blood RNA sequencing was performed in patients with advanced NSCLC receiving anti-PD-1/PD-L1 therapy (n=61) and in a control group with predominantly early-stage disease (n=29). Differential expression and functional enrichment analyses were used to characterize global and baseline transcriptomic differences, early treatment-related changes, and molecular signatures associated with NT-proBNP elevation and survival.\n\nResults: Despite substantial transcriptomic overlap (86.0% of genes shared), global analysis revealed significant differences between early- and advanced-stage disease, as demonstrated by PCA and PERMANOVA. Baseline comparison in patients who subsequently developed NT-proBNP elevation identified a small set of differentially expressed genes (n=9), indicating subtle pre-treatment differences in regulatory and signaling pathways. Early response analysis demonstrated modest transcriptional changes after the first ICI cycle, with enrichment analyses pointing to immune-related pathways, including leukocyte migration and cytokine signaling. NT-proBNP-defined phenotype was associated with exploratory differential gene expression patterns and enrichment of pathways related to T-cell activation and immune signaling. Exploratory survival-associated transcriptomic profiles were characterized by enrichment of pathways related to platelet activation, coagulation and cell adhesion.\n\nConclusion: Peripheral blood transcriptomic profiling reveals stage-dependent and clinically relevant transcriptomic patterns in NSCLC, including early immune-related transcriptional changes and signatures associated with a cardiovascular biomarker phenotype defined by NT-proBNP changes. Although these alterations are subtle, they highlight the potential of peripheral blood transcriptomic profiling to identify transcriptomic signatures associated with an NT-proBNP-defined cardiovascular biomarker phenotype. Given the exploratory nature of the analyses and the relatively small size of several subgroups, particularly the survival comparison, these findings should be interpreted as hypothesis-generating and require validation in independent cohorts.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Experimental Oncology, Laboratory of Cancer Metabolism, Maria Sklodowska-Curie National Research Institute of Oncology",
    "Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education",
    "Department of Lung Cancer and Thoracic Tumours, Maria Skłodowska-Curie National Research Institute of Oncology",
    "Cardio-Oncology Unit, Maria Skłodowska-Curie National Research Institute of Oncology",
    "Department of Surgery, Department of Thoracic Surgery, National Research Institute of Chest Diseases",
    "Department of Cardio-Oncology, Centre of Postgraduate Medical Education",
    "Maria Skłodowska-Curie National Research Institute of Oncology"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Joanna Ziemska-Legięcka"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Natalia Żeber-Lubecka"
    },
    {
      "affs": [
        2
      ],
      "name": "Magdalena Borucka"
    },
    {
      "affs": [
        3
      ],
      "name": "Dorota Kaczmarska"
    },
    {
      "affs": [
        2
      ],
      "name": "Magdalena Zaborowska-Szmit"
    },
    {
      "affs": [
        3
      ],
      "name": "Patrycja Ozdowska"
    },
    {
      "affs": [
        2
      ],
      "name": "Katarzyna Zajda"
    },
    {
      "affs": [
        2
      ],
      "name": "Anna Janowicz-Żebrowska"
    },
    {
      "affs": [
        0
      ],
      "name": "Michalina Dąbrowska"
    },
    {
      "affs": [
        4
      ],
      "name": "Lukasz Serementa"
    },
    {
      "affs": [
        4
      ],
      "name": "Tadeusz M. Orlowski"
    },
    {
      "affs": [
        2
      ],
      "name": "Maciej Krzakowski"
    },
    {
      "affs": [
        3,
        5
      ],
      "name": "Sebastian Szmit"
    },
    {
      "affs": [
        0
      ],
      "name": "Michał Mikula"
    },
    {
      "affs": [
        0
      ],
      "name": "Jerzy Ostrowski"
    },
    {
      "affs": [
        6
      ],
      "name": "Beata Jagielska"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dr9tpt3d8qp7f.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1972440",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733417/",
  "id": "dr9tpt3d8qp7f",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972440/full",
  "language": "en",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7223103025",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1972440/pdf",
  "pmcid": "PMC13733417",
  "pmid": "42985563",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dr9tpt3d8qp7f.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1972440",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1972440/full"
    },
    {
      "first_seen": "2026-11-08T12:23:12Z",
      "native_id": "PMC13733417",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1972440"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "Cardiovascular biomarker phenotype associated with immune checkpoint inhibitor therapy in patients with non-small cell lung cancer: an exploratory blood transcriptome study",
  "title_text": "Cardiovascular biomarker phenotype associated with immune checkpoint inhibitor therapy in patients with non-small cell lung cancer: an exploratory blood transcriptome study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:12Z",
  "url": "https://research.draconitic.com/paper/dr9tpt3d8qp7f",
  "venue": "Frontiers in Immunology",
  "versions": []
}