{
  "abstract": "Clear cell renal cell carcinoma (ccRCC) is characterized by marked clinical and immunological heterogeneity, and conventional clinicopathological variables do not fully capture patient survival risk. CD8+ T cells play a central role in antitumor immunity, yet their functional states can encompass both effective cytotoxic responses and dysfunctional immune programs. This study aimed to derive a survival-informed CD8+ T cell-associated gene signature and evaluate its prognostic associations, cellular expression, and relationship to immune dysfunction. Tumor-infiltrating CD8+ T cells from GSE178481 were analyzed using Semi-supervised Iterative Deep Learning for Identifying Single-cell High-Risk Populations (SIDISH) with survival information from The Cancer Genome Atlas (TCGA) training cohort. Candidate genes underwent cell-level differential expression analysis, sample-level pseudobulk screening, in silico perturbation, univariable Cox screening and benchmarking of 246 machine-learning model combinations. The final risk score was assessed for survival stratification, independent prognostic value, nomogram performance, pathway enrichment, tumor microenvironment features, and survival associations in a programmed cell death protein 1 (PD-1) blockade-treated cohort. SIDISH identified a subset of high-risk CD8+ T cells and corresponding candidate marker genes for subsequent model construction. The selected elastic net (α =0.8) plus least absolute shrinkage and selection operator (LASSO) Cox regression model generated a multigene risk score that consistently stratified overall survival (OS) in the TCGA training set, TCGA validation set, E-MTAB-1980 cohort, and CPTAC cohort. Higher risk scores were associated with advanced stage and grade and remained independently prognostic after adjustment for clinicopathological covariates in TCGA and E-MTAB-1980 cohorts. Nomograms incorporating the risk score improved individualized prediction of OS and progression-free survival (PFS). The risk score showed potential associations with immune-related pathways, metabolic pathways, and the tumor immune microenvironment, and was also associated with prognosis in the CheckMate 025 cohort. This survival-informed CD8+ T cell-associated signature was associated with prognosis in ccRCC and showed potential associations with immune features. These findings suggest that integrating single-cell immune states with bulk transcriptomic survival modeling may help identify prognosis-related signatures, although further validation is needed.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Nursing, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.",
    "Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hui Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Fan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yi Lu"
    },
    {
      "affs": [
        1
      ],
      "name": "Lifeng Ding"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1wznv5retand6.bib",
  "cited_by": 0,
  "doi": "10.21037/tcr-2026-1965",
  "fulltext_url": "https://europepmc.org/articles/PMC13743262",
  "id": "1wznv5retand6",
  "issns": [
    "2218-676X",
    "2219-6803"
  ],
  "landing_url": "https://europepmc.org/article/MED/42997734",
  "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": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2730|Cancer Immunotherapy and Biomarkers"
    ]
  ],
  "openalex": "W7224131753",
  "pdf_url": "https://europepmc.org/articles/PMC13743262?pdf=render",
  "pmcid": "PMC13743262",
  "pmid": "42997734",
  "published": "2026-09-28",
  "publisher": "AME Publications",
  "ris": "https://research.draconitic.com/paper/1wznv5retand6.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:41Z",
      "native_id": "MED:42997734",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42997734"
    },
    {
      "first_seen": "2026-11-10T12:23:57Z",
      "native_id": "PMC13743262",
      "source": "pmc",
      "url": "https://doi.org/10.21037/tcr-2026-1965"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Cancer Immunotherapy and Biomarkers",
      "subfield": "oncology"
    }
  ],
  "title": "A survival-informed CD8⁺ T cell-associated gene signature and its prognostic relevance in clear cell renal cell carcinoma.",
  "title_text": "A survival-informed CD8⁺ T cell-associated gene signature and its prognostic relevance in clear cell renal cell carcinoma.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:57Z",
  "url": "https://research.draconitic.com/paper/1wznv5retand6",
  "venue": "Translational cancer research",
  "versions": []
}