Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis

• Verfasst von: Yuan, Tanwei [VerfasserIn]
• Verfasst von: Wankhede, Durgesh [VerfasserIn]
• Verfasst von: Edelmann, Dominic [VerfasserIn]
• Verfasst von: Kather, Jakob Nikolas [VerfasserIn]
• Verfasst von: Tagscherer, Katrin E. [VerfasserIn]
• Verfasst von: Roth, Wilfried [VerfasserIn]
• Verfasst von: Bewerunge-Hudler, Melanie [VerfasserIn]
• Verfasst von: Brobeil, Alexander [VerfasserIn]
• Verfasst von: Kloor, Matthias [VerfasserIn]
• Verfasst von: Bläker, Hendrik [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Hoffmeister, Michael [VerfasserIn]
• Titel: Large-scale external validation and meta-analysis of gene methylation biomarkers in tumor tissue for colorectal cancer prognosis
• Verf.angabe: Tanwei Yuan, Durgesh Wankhede, Dominic Edelmann, Jakob Nikolas Kather, Katrin E. Tagscherer, Wilfried Roth, Melanie Bewerunge-Hudler, Alexander Brobeil, Matthias Kloor, Hendrik Bläker, Hermann Brenner, and Michael Hoffmeister
• E-Jahr: 2024
• Jahr: July 2024
• Umfang: 12 S.
• Illustrationen: Illustrationen
• Fussnoten: Online verfügbar 24 June 2024, Version des Artikels 24 June 2024 ; Gesehen am 13.01.2025
• Titel Quelle: Enthalten in: EBioMedicine
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 2014
• Jahr Quelle: 2024
• Band/Heft Quelle: 105(2024) vom: Juli, Artikel-ID 105223, Seite 1-12
• ISSN Quelle: 2352-3964
• DOI: doi:10.1016/j.ebiom.2024.105223
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Colorectal cancer
• Sach-SW: External validation
• Sach-SW: Gene methylation biomarkers
• Sach-SW: Meta-analysis
• Sach-SW: Prognosis
• K10plus-PPN: 1914415310

Abstract

Background - DNA methylation biomarkers in colorectal cancer (CRC) tissue hold potential as prognostic indicators. However, individual studies have yielded heterogeneous results, and external validation is largely absent. We conducted a comprehensive external validation and meta-analysis of previously suggested gene methylation biomarkers for CRC prognosis. - Methods - We performed a systematic search to identify relevant studies investigating gene methylation biomarkers for CRC prognosis until March 2024. Our external validation cohort with long-term follow-up included 2303 patients with CRC from 22 hospitals in southwest Germany. We used Cox regression analyses to assess associations between previously suggested gene methylation biomarkers and prognosis, adjusting for clinical variables. We calculated pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) using random-effects models. - Findings - Of 151 single gene and 29 multiple gene methylation biomarkers identified from 121 studies, 37 single gene and seven multiple gene biomarkers were significantly associated with CRC prognosis after adjustment for clinical variables. Moreover, the directions of these associations with prognosis remained consistent between the original studies and our validation analyses. Seven single biomarkers and two multi-biomarker signatures were significantly associated with CRC prognosis in the meta-analysis, with a relatively strong level of evidence for CDKN2A, WNT5A, MLH1, and EVL. - Interpretation - In a comprehensive evaluation of the so far identified gene methylation biomarkers for CRC prognosis, we identified candidates with potential clinical relevance for further investigation. - Funding - The German Research Council, the Interdisciplinary Research Program of the National Center for Tumor Diseases (NCT), Germany, the German Federal Ministry of Education and Research.