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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Genetics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1434791

Exploring the molecular profile of localized colon cancer: Insights from the AIO Colopredict Plus (CPP) Registry

Provisionally accepted
Ira Ekmekciu Ira Ekmekciu 1*Doreen M. Zucha Doreen M. Zucha 2Jens Christmann Jens Christmann 2Sarah Wisser Sarah Wisser 2Vera Heuer Vera Heuer 1Buelent Sargin Buelent Sargin 3Stephan Hollerbach Stephan Hollerbach 4Christof Lamberti Christof Lamberti 5Lothar Müller Lothar Müller 6Celine Lugnier Celine Lugnier 1Berlinda Verdoodt Berlinda Verdoodt 2Robin Denz Robin Denz 7Inke Feder Inke Feder 2Anke Reinacher-Schick Anke Reinacher-Schick 1Andrea Tannapfel Andrea Tannapfel 2Iris Tischoff Iris Tischoff 2
  • 1 St Josef Hospital, Bochum, Germany
  • 2 Institute of Pathology, Faculty of Medicine, Ruhr University Bochum, Bochum, North Rhine-Westphalia, Germany
  • 3 St Marien Hospital Lunen, Lunen, Germany
  • 4 General Hospital Celle, Celle, Germany
  • 5 Hematology and Oncology, regiomed Hospital Group, Coburg, Germany
  • 6 Onkologie UnterEms, Leer, Germany
  • 7 Department of Medical Informatics, Biometry and Epidemiology, Ruhr-University Bochum, Bochum, North Rhine-Westphalia, Germany

The final, formatted version of the article will be published soon.

    Understanding the mutational landscape of colon cancer (CC) is crucial for targeted therapy development. Microsatellite instability (MSI-H), rat sarcoma (RAS), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations (MT) are pivotal markers. Further investigation into clinicopathological features of RAS and BRAF MT in microsatellite stable (MSS) and MSI-H tumors is warranted. A retrospective analysis of 4883 localized CC patients (pts.) was conducted. Molecular profiling assessed MSI, KRAS, NRAS, and BRAF MT. Correlation with clinicopathological data employed ANOVA and Chi-square tests. Disease-free survival (DFS) and overall survival (OS) were analyzed adjusting for age, gender, sidedness, UICC stage, Charlson Comorbidity Index (CCI). A Cox model incorporated all variables as covariates. This analysis included 4883 pts. (2302 female/ male, 3865 (79.2%) MSS, 1018 (20.8%) MSI-H). MSS pts. had more All-Wild Type (WT), KRAS MT, and NRAS MT tumors vs. MSI-H pts. (42.1% vs. 21.1%; 39.8% vs. 15.4%; 3.6% vs. 0.7%; p<0.001 for each). BRAF MT tumors (95.5% BRAF V600E MT) were more prevalent in MSI-H individuals (62.8% vs. 8.1%, p<0.001). KRAS and BRAF MT tumors were more frequently rightsided, while BRAF MT tumors were associated with female gender, advanced disease stage, lymph node positivity, and poorer differentiation in the MSS subset (p<0.001). Common KRAS mutations included p.G12D (30.44%) and p.G12V (21.3%) in MSS and p.G13D (28.9%) and p.G12D (22.37%) in MSI-H. NRAS MT tumors were dominated by codon 61 mutations (51.7%). Survival analysis revealed worst prognosis in BRAF MT MSS tumors (DFS: HR 1.74 (95% CI 1.15-2.62, p=0.009; OS: HR 1.61 (95% CI 0.99-2.6), p=0.055). The 3-years DFS and 5-years OS rates were lowest in this subset (61.6% and 57.7% respectively). These findings highlight the complex interplay between molecular subtypes, clinicopathological features, and survival outcomes in early CC. Further research is needed to elucidate underlying mechanisms and develop personalized treatment strategies.

    Keywords: Colon Cancer, localized, Real world data, Microsatellite Instability, Ras, BRAF

    Received: 18 May 2024; Accepted: 11 Sep 2024.

    Copyright: © 2024 Ekmekciu, Zucha, Christmann, Wisser, Heuer, Sargin, Hollerbach, Lamberti, Müller, Lugnier, Verdoodt, Denz, Feder, Reinacher-Schick, Tannapfel and Tischoff. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ira Ekmekciu, St Josef Hospital, Bochum, Germany

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