Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.
- 1Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden. [email protected].
- 2Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
- 3Department of Diagnostics and Intervention, Oncology, Umeå University, Umeå, Sweden.
Abstract
Background and purpose
Co-occurring mutations in lung cancer can influence disease progression and treatment response. Understanding these patterns may refine prognostic stratification and therapeutic decisions.Patients/materials and methods
We analysed targeted sequencing data from 528 North Swedish non-small cell lung cancer (NSCLC) patients, validating findings in 2,239 global patients. Co-mutation enrichment was assessed using the Fisher's exact test with odds ratios, and survival associations were evaluated using Kaplan-Meier/log-rank analyses and Cox models.Results
The North Sweden cohort showed non-random co-mutation patterns shaped by pathway dependencies. The combination of Kirsten rat sarcoma virus oncogene homolog (KRAS) and STK11 co-mutation was significantly enriched in both North Sweden (p = 4.7 × 10-4) and globally (p = 2.5 × 10-22), with North Sweden co-mutants showing significantly worse survival compared with KRAS-only cases (p = 0.037). Epidermal growth factor receptor (EGFR)+phosphate and tensin homolog (PTEN) co-mutation was significantly associated with poorer survival in both cohorts (North Sweden: p = 0.013; World: p = 0.0013). EGFR+TP53 co-mutation trended towards poorer survival compared with EGFR alone, reaching significance globally (p = 1.4 × 10-5). Adenomatous polyposis coli (APC) and PTEN were positively enriched in North Sweden (p = 0.018), and co-mutants had worse survival than APC-only cases (p = 0.029), a pattern mirrored globally. KRAS+TP53 was a frequent co-mutation but not prognostically significant. KRAS and EGFR were strongly mutually exclusive in both cohorts.Interpretation
Pathway-level co-mutation interactions, rather than individual mutation burden, drive survival heterogeneity in lung cancer. Specific co-mutations, such as KRAS+STK11 and APC+PTEN, are enriched and linked to worse survival, supporting the clinical relevance of co-mutation analysis in NSCLC.
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BibTeX
@article{karlowatz2026comutation,
title = {{Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.}},
author = {Nicholas Karlowatz and Linda Köhn and Cedric Patthey and Jonas Nilsson and Mikael Johansson},
journal = {Acta oncologica (Stockholm, Sweden)},
year = {2026},
month = oct,
doi = {10.2340/1651-226x.2026.46330},
url = {https://europepmc.org/article/MED/42852590},
note = {CC BY},
}
RIS
TY - JOUR
TI - Co-mutation patterns and survival associations in lung cancer: a comparative analysis of Swedish and global cohorts.
AU - Nicholas Karlowatz
AU - Linda Köhn
AU - Cedric Patthey
AU - Jonas Nilsson
AU - Mikael Johansson
PY - 2026
DA - 2026/10/09
JO - Acta oncologica (Stockholm, Sweden)
DO - 10.2340/1651-226x.2026.46330
UR - https://europepmc.org/article/MED/42852590
AB - Background and purpose Co-occurring mutations in lung cancer can influence disease progression and treatment response. Understanding these patterns may refine prognostic stratification and therapeutic decisions.Patients/materials and methods We analysed targeted sequencing data from 528 North Swedish non-small cell lung cancer (NSCLC) patients, validating findings in 2,239 global patients. Co-mutation enrichment was assessed using the Fisher's exact test with odds ratios, and survival associations were evaluated using Kaplan-Meier/log-rank analyses and Cox models.Results The North Sweden cohort showed non-random co-mutation patterns shaped by pathway dependencies. The combination of Kirsten rat sarcoma virus oncogene homolog (KRAS) and STK11 co-mutation was significantly enriched in both North Sweden (p = 4.7 × 10-4) and globally (p = 2.5 × 10-22), with North Sweden co-mutants showing significantly worse survival compared with KRAS-only cases (p = 0.037). Epidermal growth factor receptor (EGFR)+phosphate and tensin homolog (PTEN) co-mutation was significantly associated with poorer survival in both cohorts (North Sweden: p = 0.013; World: p = 0.0013). EGFR+TP53 co-mutation trended towards poorer survival compared with EGFR alone, reaching significance globally (p = 1.4 × 10-5). Adenomatous polyposis coli (APC) and PTEN were positively enriched in North Sweden (p = 0.018), and co-mutants had worse survival than APC-only cases (p = 0.029), a pattern mirrored globally. KRAS+TP53 was a frequent co-mutation but not prognostically significant. KRAS and EGFR were strongly mutually exclusive in both cohorts.Interpretation Pathway-level co-mutation interactions, rather than individual mutation burden, drive survival heterogeneity in lung cancer. Specific co-mutations, such as KRAS+STK11 and APC+PTEN, are enriched and linked to worse survival, supporting the clinical relevance of co-mutation analysis in NSCLC.
SN - 0284-186X
SN - 1651-226X
ER -