{
  "abstract": "Proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer (CRC) constitutes the predominant molecular subgroup of CRC and usually shows limited benefit from immune checkpoint blockade. This study aimed to characterize immunogenic cell death (ICD)-associated transcriptomic patterns and develop an ICD-related prognostic model for pMMR/MSS CRC. Public gene-expression profiles and clinical annotations were retrieved from the Gene Expression Omnibus (GEO). The GSE39582-pMMR cohort was used for subtype identification and model development (n=459), and eligible pMMR/MSS cases from GSE143985 and GSE92921 were combined for external validation (n=132). Thirty-four ICD-related genes were used for consensus clustering. Differential expression analysis, functional enrichment analysis, Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE), single-sample gene set enrichment analysis, immune checkpoint and human leukocyte antigen (HLA) assessment, Tumor Immune Dysfunction and Exclusion (TIDE) prediction, Kaplan-Meier analysis, least absolute shrinkage and selection operator (LASSO) Cox regression, time-dependent receiver operating characteristic (ROC) analysis, and Cox proportional hazards models were applied. Consensus clustering divided the GSE39582-pMMR cohort into ICD-high (n=155) and ICD-low (n=304) subtypes. The ICD-high subtype showed higher immune and stromal scores, lower tumor purity, broader immune-cell infiltration, and increased expression of checkpoint and HLA genes, although overall survival did not differ significantly between subtypes. Subtype-related genes were enriched in immune response, leukocyte migration, chemokine and complement activity, adhesion, and extracellular matrix pathways. A seven-gene model consisting of CASP1, IL1R1, IL6, MYD88, NT5E, P2RX7, and PIK3CA stratified patients with significantly different overall survival in the development cohort and showed an unfavorable disease-free survival trend in the external validation cohort. Higher risk scores were associated with myeloid immunosuppressive infiltration and TIDE-defined non-response. Multivariate Cox analysis identified the risk score as an independent prognostic factor. ICD-associated transcriptional patterns identified immune-distinct subtypes in pMMR/MSS CRC and yielded a prognostic signature associated with survival and predicted immunotherapy response. The ICD-high subtype showed an immune-infiltrated but immunosuppression-associated phenotype, supporting further investigation of ICD-related models for risk stratification and treatment-response estimation in pMMR/MSS CRC.",
  "abstract_shown": true,
  "affiliations": [
    "Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jia He"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinxiu Qu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuan Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Pinxu Ge"
    },
    {
      "affs": [
        0
      ],
      "name": "Shijie Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiqiang Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Benqiang Rao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4rsj72hcgh7vm.bib",
  "cited_by": 0,
  "doi": "10.21037/jgo-2026-0748",
  "fulltext_url": "https://europepmc.org/articles/PMC13740570",
  "id": "4rsj72hcgh7vm",
  "issns": [
    "2078-6891",
    "2219-679X"
  ],
  "landing_url": "https://europepmc.org/article/MED/42996609",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224137227",
  "pdf_url": "https://europepmc.org/articles/PMC13740570?pdf=render",
  "pmcid": "PMC13740570",
  "pmid": "42996609",
  "published": "2026-09-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4rsj72hcgh7vm.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42996609",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42996609"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "An immunogenic cell death-related classification for prognostic stratification and immunotherapy response prediction in proficient mismatch repair/microsatellite stable colorectal cancer.",
  "title_text": "An immunogenic cell death-related classification for prognostic stratification and immunotherapy response prediction in proficient mismatch repair/microsatellite stable colorectal cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:41Z",
  "url": "https://research.draconitic.com/paper/4rsj72hcgh7vm",
  "venue": "Journal of gastrointestinal oncology",
  "versions": []
}