Plasma miRNA‐based signatures in CRC screening programs
| Autor: | Gabriele Delconte, Gabriella Sozzi, Giovanni Rubis Passoni, Massimo Primignani, L. Fazzini, Susanna Zanutto, Manuela Gariboldi, Roberta Ilaria Olimpia Motta, Enzo Masci, Cristiano Crosta, Marco A. Pierotti, Antonino Belfiore, Laura Tizzoni, Valentina Dall'Olio, Marco Dal Fante, Aldo Airoldi, Chiara Maura Ciniselli, Francesca Iannuzzi, Francesca Turpini, P. Viaggi, Luigi Bisanti, Giuseppe De Roberto, Emanuele Meroni, Marcello Vangeli, Anna Maria Cantù, Paolo Verderio, Giulia Tosetti, Monica Arena, Andrea Cassinotti, Mara Lecchi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Colorectal cancer Colonoscopy 03 medical and health sciences 0302 clinical medicine Internal medicine Cancer screening Humans Medicine Prospective cohort study Early Detection of Cancer Aged medicine.diagnostic_test business.industry Cancer Middle Aged medicine.disease MicroRNAs 030220 oncology & carcinogenesis Cohort Female Cancer biomarkers Colorectal Neoplasms business Blood sampling |
| Zdroj: | International Journal of Cancer. 146:1164-1173 |
| ISSN: | 1097-0215 0020-7136 |
| Popis: | Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607-0.682), 0.670 (0.626-0.714) and 0.682 (0.580-0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most. |
| Databáze: | OpenAIRE |
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