{
  "abstract": "Background: Acrolein is a highly reactive aldehyde generated endogenously during lipid peroxidation and encountered through environmental and dietary exposures. Although acrolein has established electrophilic, genotoxic, and oxidative-stress effects, the extent to which acrolein-linked gene perturbation is represented in colorectal cancer (CRC) transcriptomes and relates to tumor immune-stromal heterogeneity remains incompletely characterized.\n\nMethods: We integrated direct human acrolein target evidence from the Comparative Toxicogenomics Database (CTD) with TCGA-COAD/READ bulk RNA-sequencing profiles and a single-cell RNA-sequencing subset from GSE231559. The CTD curation yielded 179 unique direct human targets. Bulk analyses included 624 primary-tumor and 51 solid-tissue normal profiles. Single-cell analyses included six tumor and three normal libraries, yielding 24,128 retained cells assigned to eight broad marker-supported compartments. Target dysregulation burden, immune-stromal expression programs, and library-aware single-cell target localization were evaluated as transcriptomic summaries. In addition, RT-qPCR was performed in HCT 116 colorectal carcinoma cells to experimentally evaluate four measurable CTD targets (NFKBIA, GSTP1, VIM, and GPX4) after acrolein exposure.\n\nResults: The bulk tumor-normal analysis identified 5,594 differentially expressed genes at FDR < 0.05 and |log2 fold change| ≥ 1. Of 179 CTD acrolein targets, 155 were measurable in the bulk dataset and 43 met the differential-expression threshold. Mean absolute normal-reference target burden was higher in tumors than normal tissue (1.96 vs. 0.75; difference 1.21; Welch p = 3.62e-42). Within primary tumors, target burden correlated negatively with T-cell and endothelial programs (rho = −0.27 for each), myeloid (rho = −0.20), fibroblast-ECM (rho = −0.19), and antigen-presentation programs (rho = −0.20), and positively with cell cycle (rho = 0.20). In single-cell data, descriptive mean target scores were highest in myeloid cells (0.455), fibroblasts (0.424), and endothelial cells (0.344). Cross-scale effects for 154 shared targets showed modest concordance (rho = 0.31, p = 6.95e-05). RT-qPCR showed vehicle-normalized relative expression of 2.18 ± 0.14 for NFKBIA, 1.83 ± 0.13 for GSTP1, 1.57 ± 0.15 for VIM, and 0.71 ± 0.09 for GPX4 after acrolein exposure (mean ± SD of three biological replicates).\n\nConclusions: Acrolein target-linked expression perturbation is detectable in CRC and is associated with immune-stromal heterogeneity across bulk and single-cell transcriptomic scales. RT-qPCR provides targeted experimental support for acrolein-responsive expression changes in NFKBIA, GSTP1, VIM, and GPX4 in HCT 116 cells. These findings support a toxicogenomic framework for hypothesis generation but do not measure acrolein exposure in patients, establish causal toxicological effects in human tumors, or demonstrate a specific intercellular signaling mechanism. Additional mechanistic, protein/adduct, dose-response, and independent-cohort validation will be required to determine the biological significance of the observed associations.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastrointestinal Surgery, The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gongming Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Liuqun Shan"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenjie Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Xucheng Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuewen Tao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianbo Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/a5amdphesx96s.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1929802",
  "fulltext_url": "https://europepmc.org/articles/PMC13713698",
  "id": "a5amdphesx96s",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1929802/full",
  "language": "eng",
  "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",
      "1306|Carcinogens and Genotoxicity Assessment"
    ]
  ],
  "openalex": "W7221816367",
  "pdf_url": "https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2026.1929802/pdf",
  "pmcid": "PMC13713698",
  "pmid": "42952972",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/a5amdphesx96s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.3389/fcvm.2026.1929802",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1929802/full"
    },
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42952972",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952972"
    },
    {
      "first_seen": "2026-10-31T12:24:12Z",
      "native_id": "PMC13713698",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcvm.2026.1929802"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Carcinogens and Genotoxicity Assessment",
      "subfield": "oncology"
    }
  ],
  "title": "Acrolein target-linked toxicological perturbation and tumor-immune microenvironment heterogeneity in colorectal cancer",
  "title_text": "Acrolein target-linked toxicological perturbation and tumor-immune microenvironment heterogeneity in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:19Z",
  "url": "https://research.draconitic.com/paper/a5amdphesx96s",
  "venue": "Frontiers in Cardiovascular Medicine",
  "versions": []
}