6 - NEW EPIGENETIC BIOMARKERS AND MOLECULAR SIGNIFICANCE IN COLORECTAL CANCER AND OBESITY
1IBIMA-Plataforma BIONAND, Málaga. 2Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Institute of Biomedical Research in Malaga-Bionand Platform, University of Málaga. 3Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigación Sanitaria de Santiago de Compostela, Complejo Hospitalario Universitario de Santiago de Compostela. 4Unidad de Gestión Clínica de Medicina Interna, Lipids and Atherosclerosis Unit, Maimonides Institute for Biomedical Research in Córdoba, Reina Sofia University Hospital, University of Córdoba.
Introduction: This study hypothesized that investigating the promoter methylation of SFRP2 gene in various biological samples from patients with CRC could offer novel biomarker utility.
Methods: The study examined SFRP2 gene expression and methylation in both healthy individuals and CRC patients with and without obesity. We assessed the comprehensive biomarker description value of SFRP2 in CRC, validated SFRP2 expression and methylation in diverse biological tissues, and evaluated its potential role as a biomarker in CRC. Furthermore, we investigated the effects of rhSFRP2 on cell proliferation, migration, and the expression of key genes associated with carcinogenesis and the Wnt pathway.
Results: SFRP2 promoter methylation in whole blood significantly predicted cancer stage, lymph node invasion, and cancer recurrence in CRC patients (p < 0.05). The global SFRP2 gene was found to be hypomethylated in CRC (p < 0.001), and these results were validated in the TCGA-COAD and TCGA-READ cohorts. Promoter SFRP2 DNA methylation was responsive to chemotherapy, with treated CRC patients exhibiting lower SFRP2 methylation compared to untreated CRC patients (p < 0.001). Low promoter SFRP2 methylation in untreated patients was linked to poor overall survival (p < 0.05). In a functional analysis of a cell system, rhSFRP2 treatment in HCT116 cells restrained cell proliferation and migration, and led to the downregulation of the AXIN2 gene, which is implicated in the Wnt signaling pathway.
Conclusions: These findings establish SFRP2 as a prospective gene in CRC, with potential utility in clinical settings, and provide molecular insights into its involvement in colorectal carcinogenesis, offering novel therapeutic approaches for CRC.
Funding: Grants from ISCIII (PI18/01399, PI21/00633). HB and LA by Sara Borrell postdoctoral contract (CD22/00053 and CD21/000131 respectively). M.M.G. by Nicolas Monardes Programme from the “Servicio Andaluz de Salud, Junta de Andalucía”, Spain (RC-0001-2018).
