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Plasma miRNA‐based signatures in CRC screening programs
Author(s) -
Zanutto Susanna,
Ciniselli Chiara Maura,
Belfiore Antonino,
Lecchi Mara,
Masci Enzo,
Delconte Gabriele,
Primignani Massimo,
Tosetti Giulia,
Dal Fante Marco,
Fazzini Linda,
Airoldi Aldo,
Vangeli Marcello,
Turpini Francesca,
Rubis Passoni Giovanni Giuseppe,
Viaggi Paolo,
Arena Monica,
Motta Roberta Ilaria Olimpia,
Cantù Anna Maria,
Crosta Cristiano,
De Roberto Giuseppe,
Iannuzzi Francesca,
Cassinotti Andrea,
Dall'Olio Valentina,
Tizzoni Laura,
Sozzi Gabriella,
Meroni Emanuele,
Bisanti Luigi,
Pierotti Marco Alessandro,
Verderio Paolo,
Gariboldi Manuela
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32573
Subject(s) - medicine , colorectal cancer , colonoscopy , cohort , cancer , prospective cohort study , confidence interval , oncology , adenoma , blood test , receiver operating characteristic , gastroenterology
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.