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Peer-reviewedCC BYClinical & experimental metastasis

Molecular, histopathological, and clinical risk factors for overall metastatic disease and brain metastases in surgically resected stage I-III lung cancer.

  • Anne Pernille Harlem Dyrbekk1,2,3
  • Pål Suhrke4
  • Marianne Odnakk Ludahl5
  • Nermin Zecic5
  • Joakim Oliu Moe6
  • Inger Johanne Zwicky Eide7,8
  • Marius Lund-Iversen9
  • Odd Terje Brustugun10,7,8
10 affiliations
  1. 1University of Oslo, Oslo, 0316, Norway. [email protected].
  2. 2Department of Pathology, Vestfold Hospital Trust, Tønsberg, 3103, Norway. [email protected].
  3. 3Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway. [email protected].
  4. 4Department of Pathology, Vestfold Hospital Trust, Tønsberg, 3103, Norway.
  5. 5Department of Microbiology, Division for gene-technology, Vestfold Hospital Trust, Tønsberg, 3103, Norway.
  6. 6Department of Gastroenterology, Vestfold Hospital Trust, Tønsberg, 3103, Norway.
  7. 7Department of Cancer Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, 0310, Norway.
  8. 8Department of Oncology, Vestre Viken Hospital Trust, Drammen, 3004, Norway.
  9. 9Department of Pathology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo, 0310, Norway.
  10. 10University of Oslo, Oslo, 0316, Norway.
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Abstract

Lung cancer remains a major cause of cancer-related mortality, including among patients diagnosed with potentially curable disease. Current decisions regarding perioperative treatment and follow-up rely on a limited number of established prognostic factors. Further knowledge is needed regarding the clinical, histopathological, and molecular factors associated with subsequent metastatic disease, particularly brain metastasis (BM), which is associated with poor prognosis. We investigated these factors in a large cohort of patients with surgically resected stage I-III lung cancer followed for more than five years. BM was associated with higher pathological tumour and lymph-node stage and younger age at surgery. Lung adenocarcinoma was associated with a higher risk of BM than lung squamous cell carcinoma. Several molecular alterations were associated with metastatic disease or BM, including KRAS mutations in lung adenocarcinoma and NFE2L2 mutations in lung squamous cell carcinoma. Additional associations involving specific EGFR and KRAS mutation subtypes and rarer alterations were observed, but were based on small numbers of cases and should be considered exploratory. Several of the associated genes are involved in the RAS/MAPK, PI3K/AKT/mTOR, or NRF2-related pathways. However, pathway activation and causality could not be established in this observational study. These findings support further investigation of clinical, histopathological, and molecular factors associated with metastatic progression after surgical resection. Validation in larger, independent, stage-stratified and contemporary cohorts with comprehensive treatment data is required before the identified molecular alterations can be considered for clinical risk stratification or surveillance.

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Cite

BibTeXRIS
BibTeX
@article{dyrbekk2026molecular,
  title = {{Molecular, histopathological, and clinical risk factors for overall metastatic disease and brain metastases in surgically resected stage I-III lung cancer.}},
  author = {Anne Pernille Harlem Dyrbekk and Pål Suhrke and Marianne Odnakk Ludahl and Nermin Zecic and Joakim Oliu Moe and Inger Johanne Zwicky Eide and Marius Lund-Iversen and Odd Terje Brustugun},
  journal = {Clinical \& experimental metastasis},
  year = {2026},
  month = oct,
  doi = {10.1007/s10585-026-10444-8},
  url = {https://europepmc.org/article/MED/42909660},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Molecular, histopathological, and clinical risk factors for overall metastatic disease and brain metastases in surgically resected stage I-III lung cancer.
AU  - Anne Pernille Harlem Dyrbekk
AU  - Pål Suhrke
AU  - Marianne Odnakk Ludahl
AU  - Nermin Zecic
AU  - Joakim Oliu Moe
AU  - Inger Johanne Zwicky Eide
AU  - Marius Lund-Iversen
AU  - Odd Terje Brustugun
PY  - 2026
DA  - 2026/10/23
JO  - Clinical & experimental metastasis
DO  - 10.1007/s10585-026-10444-8
UR  - https://europepmc.org/article/MED/42909660
AB  - Lung cancer remains a major cause of cancer-related mortality, including among patients diagnosed with potentially curable disease. Current decisions regarding perioperative treatment and follow-up rely on a limited number of established prognostic factors. Further knowledge is needed regarding the clinical, histopathological, and molecular factors associated with subsequent metastatic disease, particularly brain metastasis (BM), which is associated with poor prognosis. We investigated these factors in a large cohort of patients with surgically resected stage I-III lung cancer followed for more than five years. BM was associated with higher pathological tumour and lymph-node stage and younger age at surgery. Lung adenocarcinoma was associated with a higher risk of BM than lung squamous cell carcinoma. Several molecular alterations were associated with metastatic disease or BM, including KRAS mutations in lung adenocarcinoma and NFE2L2 mutations in lung squamous cell carcinoma. Additional associations involving specific EGFR and KRAS mutation subtypes and rarer alterations were observed, but were based on small numbers of cases and should be considered exploratory. Several of the associated genes are involved in the RAS/MAPK, PI3K/AKT/mTOR, or NRF2-related pathways. However, pathway activation and causality could not be established in this observational study. These findings support further investigation of clinical, histopathological, and molecular factors associated with metastatic progression after surgical resection. Validation in larger, independent, stage-stratified and contemporary cohorts with comprehensive treatment data is required before the identified molecular alterations can be considered for clinical risk stratification or surveillance.
SN  - 0262-0898
SN  - 1573-7276
ER  -