NOVEL METHYLATION-BASED BIOMARKERS FOR COLORECTAL CANCER DETECTION

VAQUER, CINTIA; GARCIA SAMARTINO, CLARA; BOCANEGRA, VICTORIA; ARBONA, SEBASTIAN; RODRIGO MILITELLO; ONGAY, RODRIGO; VALDEMOROS, PAULA; SANGUINETTI GUILLERMO; AGUSTÍN CORREA; PELLEGRINI, PABLO; MINATTI WALTER; CAMPOY, EMANUEL MARTIN

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

Sociedad Argentina de Investigaciones Clínicas

Epigenetic marks refer to chemical DNA modifications that do notaffect the DNA sequence but can modify gene expression. They aredescribed early in the tumorigenic process and can be used as biomarkers,for example, for early cancer detection. We developed abioinformatic algorithm that identifies and hierarchies sensitive andspecific epigenetic biomarkers. Currently, we are developing a PCRbasedtechnology capable of detecting biomarkers with high sensitivity,either individually or combined in the same reaction. Objective:Identify and detect methylation-based biomarkers in DNA extractedfrom tumors derived from colorectal cancer (CRC) patients. Methods:We developed a bioinformatic platform capable of implementingan algorithm that identifies methylation-based biomarkers frompublic databases (TCGA). We constituted an average risk CRCpatients prospective cohort, who attended for video colonoscopyand/or CRC resection surgery. We isolated DNA from the tumorand paired colonic normal tissue distant from the lesion. We used aPCR-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 accuratelyidentified already described biomarkers and we also identifiedour own panel of new biomarkers. Applying our own technology, wedetected SEPT9 methylation in DNA tumor tissue patients from 20CCR patients. We applied a ROC analysis obtaining an Area Underthe Curve (AUC) of 0.98, which means a high sensitive and specificdetection. As controls, we used paired colonic normal tissue. Finally,we chose the best ranked biomarkers identified by the bioinformaticplatform that were detected in the same samples, either individuallyor combined as a biomarker panel in the same PCR reaction(AUC=0.995). Conclusion: We identified and detected a panel ofnew methylation-based biomarkers that might be implemented incolorectal cancer screening.