Résumé
Abstract only e13146 Background: Following works on the clinical potentials of circulating DNA (cfDNA), our group is now particularly focused on evaluating its potential for early detection of cancer. We recently developed a test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Methods: We recently developed a screening test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Results: We are currently carrying out an extensive evaluation of this test in plasma samples from diagnosed and healthy individuals. Preliminary results on the plasma of 289 healthy subjects and 1,200 patients with various types of cancer (colorectal, breast, lung, liver, pancreatic, ovarian) of all stages, revealed a high potential with an AUC of 0.82 (0.78-0.84, 95% confidence interval, CI) and 70% sens. with 78% spe.. In breast cancer (N = 169), an AUC of 0.82 (0.78-0.86, 95% CI) with 72% sens. and 80% spe. were observed. In all stages CRC patients (N = 887), the results showed an AUC of 0.81 (0.78-0.84, 95%, CI) and 68% sens. with 80% spe.; for CRC stages 0/I/II (N = 249), an AUC of 0.75 (0.71-0.80, 95% CI) and 60% sens. with 79% spe.; and for CRC stage IV (N = 101), a 0.86 AUC (0.82-0.91, 95% CI) with 81% sens. and 78% spe.. When combining the MNR test to a threshold value of the total concentration of cfDNA (AUC = 0.82 (0.79-0.84, 95% CI), 70% sens. and 80% spe. in all stage cancers (N = 1078)), in CRC stages 0/I/II (N = 249) vs Healthy Individuals (N = 289), we observed a 63% sens. with 84% spe. Conclusions: Furthermore we recently discovered that cfDNA fragmentation, as determined by Whole Genome Sequencing using either double or single strand library, is also a parameter enabling discrimination between healthy and cancer individuals. Data on a multi-parametric test combining total cfDNA quantification, MNR and fragmentation biomarkers with help of a ongoing decision tree algorithm in machine learning will be presented during the meeting. Our on-going data suggest that our strategy in targeting cfDNA quantitative/structural features might be powerful for cancer screening/early detection and appears as an alternative or a synergistic combination to searching mutations.