Technological Platform Development for Early Cancer Detection, Towards a Focused Multi-Cancer Detection

VAQUER, CINTIA; GARCIA SAMARTINO, CLARA; BOCANEGRA, VICTORIA; ARBONA, SEBASTIAN; ONGAY, RODRIGO; PÉREZ RAVIER, ROBERTO; MANZINO, RICARDO NICOLAS; SARRIO, LEANDRO; RODRIGO, MILITELLO; CAMPOY, EMANUEL MARTIN

Madrid

Congreso; 5th Annual Congress Liquid Biopsy; 2023

International Society of Liquid Biopsy

Introduction: Early cancer detection is widely recognized as a life-saving oppor tunity. However, it is crucial to consider that cancer comprises a diverse group of diseases that share molecular bases while exhibiting variations indiagnosis, prognosis, and treatment based on their anatomical origin. In light of this perspective, developing technologies that enable early detection of these pathologies, in a clinically meaningful manner, becomes highly pertinent.Methods: We accomplished a bioinformatic platform capable of identifying methylation-based biomarkers for different tumor types using open access databases. Our research has successfully revealed these biomarker’s presence in DNA extracted from tissue samples obtained from patients diagnosed with colorectal cancer (CRC) and hepatocellular carcinoma (HCC). To facilitate detection, we performed our proprietary qPCR-based technology, allowing the simultaneous identification of multiple biomarkers. Additionally, we utilized one of our exclusive biomarker panels to detect CRC in 40 plasma samples from healthy individuals and cancer patients, employing ddPCR.Results: Initially, we identified 275 candidate CpG sites for CRC and 96 CpG sites for HCC. Employing different classification criteria, we tailored distinct detection panels for each tumor type (between 3 and 6 biomarkers per panel). Through our qPCR-based technology, we successfully validated our bioinformatic platform by detecting individual and combined biomarkers in 40 tissue samples collected from CRC patients and 20 from HCC patients. After biomarker panels validation, we engineered an early-stage prototype diagnostic test ddPCR-based (initially for CRC). This prototype allows the detection of a three biomarker panel in circulant DNA samples. To further verify its accuracy, we validated the prototype using plasma samples obtained from 20CRC patients and 20 healthy individuals. Our results demonstrated an overall AUC of 0,91, accompanied by a 80% sensitivity (95% CI: 58.40% to 91.93%) and a 90% specificity (95% CI: 69.9% to 98.22%).Conclusion: Through our validation process, we successfully achieved a PCR-based technology capable of detecting methylation-based biomarker panels in liquid biopsies. Although the initial panel was validated in CRC patients, the versatility of our technology allows it to detect different tumor types panels simultaneously, with the potential to be implemented in a focused multi-cancertest.