Abstract
Accurate identification of which patients with early (T1) colon cancer (CC) have lymph node metastases (LNM) is a major challenge. Current strategies have limited accuracy, resulting in overtreatment of > 80% of patients. Whilst gene expression profiles (GEPs) have shown promise in identifying patients with LNM in early studies, these have not become a routine part of clinical practice. A limitation of these GEPs is that they are generic and so agnostic of other factors that could influence gene expression, such as tumour location and mismatch repair (MMR) status. In a retrospective translational study of 24 patients who underwent surgery for T1 CC, we demonstrate that both tumour location and MMR status have a significant impact on intratumoural gene expression. This impact was seen in patients with and without LNM. When compared to analyses of all patients, side-specific and MMR status-specific analyses revealed a higher number of differentially expressed genes with lower false discovery rates. Several interesting candidate genes for LNM were identified, including AHNAK, ATG12 and DMBT1. These findings demonstrate the influence of tumour location and MMR status on intratumoural gene expression in T1 CC and highlights the need to account for these factors when developing GEPs for clinical translation.
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The current study was supported by the Arvid Nilsson’sFoundation, Bispebjerg and Frederiksberg Hospitals’ Internal Research Grants,the Else and Mogens Wedell-Wedellsborg’s Foundation, the Inge and JørgenLarsen’s Memorial Foundation, the Meirion Thomas Cancer Research Trust,and the NEYE Foundation. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of themanuscript, or in the decision to publish the results.
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Dr. Krarup has received personal fees and served as proctor and speaker for Intuitive Surgical and received a research grant from Pharmacosmos A/S. Professor Litman is funded by LEO Pharma A/S. Dr Smith has received research grants from The Lundbeck Foundation, The Novo Nordisk Foundation, and The NEYE Foundation. The remaining authors declare no conflicts of interest.
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Ebbehøj, A.L., Jørgensen, L.N., Chiranth, D. et al. Tumour location and mismatch repair status impact gene expression profiles associated with lymph node metastases in T1 colon cancers. Sci Rep (2026). https://doi.org/10.1038/s41598-026-52722-1
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DOI: https://doi.org/10.1038/s41598-026-52722-1
