{
  "abstract": "Background/Objectives: We evaluated molecular selection stability and external prediction beyond age, sex and broad pathological stage in resected stage I–II lung adenocarcinoma. Methods: Models were developed in 228 patients from two sources and frozen before evaluation in four historical cohorts containing 778 patients. The primary comparison added pathway scores using elastic-net Cox regression. Secondary analyses examined a gene model, 200 development bootstrap resamples, alternative modeling specifications and locally updated baselines. Prediction error was measured by the integrated Brier score over 1–3 years (IBS); negative molecular-minus-clinical differences (ΔIBS) favored molecular models. Evaluation intervals used 2000 paired bootstrap resamples. Results: The pathway model retained no molecular terms. The final gene model retained 16 genes, whereas both source-held-out fits and 159/200 development resamples retained none. Penalties of 0.5, 0.15 and 0.05 were selected in 160, 38 and 2 resamples. Alternative specifications changed gene retention from 0 to 61 and pathway retention from 0 to 5. Frozen gene-model ΔIBS ranged from −0.0034 to 0.0055 across cohorts. Its equal cohort mean was 0.0016 (95% CI, −0.0012 to 0.0042), compared with −0.0008 (−0.0024 to 0.0007) after cross-fitted local baseline updating. The clinical model predicted a 3-year mortality of 19.6% in Japan and 22.6% in Moffitt, versus observed values of 9.1% and 28.6%. Conclusions: Molecular selection was unstable, and incremental performance depended on specification and population. The results characterize these learning procedures and their limited development sample; broader transcriptomic prognostic value and contemporary clinical utility remain unestablished.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Statistics and Data Science, Cornell University, Ithaca, NY 14853, USA",
    "Department of Pulmonary and Critical Care Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China",
    "Senior Department of Pulmonary and Critical Care Medicine, The Eighth Medical Center of Chinese PLA General Hospital, Beijing 100091, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhihao Lei"
    },
    {
      "affs": [
        1
      ],
      "name": "Chenxi Zou",
      "orcid": "0009-0005-0481-3863"
    },
    {
      "affs": [
        2
      ],
      "name": "Wei Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bm199s1j8q7vc.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18203361",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702175/?tool=EBI",
  "id": "bm199s1j8q7vc",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/20/3361",
  "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": [
    [
      "openalex",
      "2730|Lung Cancer Research Studies"
    ]
  ],
  "openalex": "W7222978727",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702175/pdf/?tool=EBI",
  "pmcid": "PMC13702175",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/bm199s1j8q7vc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18203361",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/20/3361"
    },
    {
      "first_seen": "2026-10-30T12:21:47Z",
      "native_id": "PMC:PMC13702175",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702175"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Lung Cancer Research Studies",
      "subfield": "oncology"
    }
  ],
  "title": "Selection Instability and External Performance of Transcriptomic Models Beyond Age, Sex and Stage in Resected Lung Adenocarcinoma",
  "title_text": "Selection Instability and External Performance of Transcriptomic Models Beyond Age, Sex and Stage in Resected Lung Adenocarcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:47Z",
  "url": "https://research.draconitic.com/paper/bm199s1j8q7vc",
  "venue": "Cancers",
  "versions": []
}