NOVEL METHYLATION-BASED BIOMARKERS FOR COLORECTAL CANCER DETECTION

VAQUER CC; GARCÍA SAMARTINO C; BOCANEGRA V; ARBONA S; MILITELLO RD; ONGAY RL; VALDEMOROS P; SANGUINETTI G; CORREA A; PELLEGRINI A; MINATTI W; CAMPOY EM

Mar del Plata

Congreso; Sociedad Argentina de Investigación Clínica, Reunión Anual de Sociedades de Biociencias; 2022

Sociedad Argentina de Investigación Clínica

Epigenetic marks refer to chemical DNA modifications that do not affect the DNA sequence but can modify gene expression. They are described early in the tumorigenic process and can be used as biomarkers, for example, for early cancer detection. We developed a bioinformatic algorithm that identifies and hierarchies sensitive and specific epigenetic biomarkers. Currently, we are developing a PCRbased technology capable of detecting biomarkers with high sensitivity, either individually or combined in the same reaction. Objective: Identify and detect methylation-based biomarkers in DNA extracted from tumors derived from colorectal cancer (CRC) patients. Methods: We developed a bioinformatic platform capable of implementing an algorithm that identifies methylation-based biomarkers from public databases (TCGA). We constituted an average risk CRC patients prospective cohort, who attended for video colonoscopy and/or CRC resection surgery. We isolated DNA from the tumor and paired colonic normal tissue distant from the lesion. We used a PCR-based technology to detect a well know epigenetic biomarker (SEPT9) for CRC screening and our proprietary biomarkers. Results: initially, we validated the bioinformatic platform since it accurately identified already described biomarkers and we also identified our own panel of new biomarkers. Applying our own technology, we detected SEPT9 methylation in DNA tumor tissue patients from 20 CCR patients. We applied a ROC analysis obtaining an Area Under the Curve (AUC) of 0.98, which means a high sensitive and specific detection. As controls, we used paired colonic normal tissue. Finally, we chose the best ranked biomarkers identified by the bioinformatic platform that were detected in the same samples, either individually or combined as a biomarker panel in the same PCR reaction (AUC=0.995). Conclusion: We identified and detected a panel of new methylation-based biomarkers that might be implemented in colorectal cancer screening.