Plasma miRNA-based signatures in CRC screening programs

Susanna Zanutto, Chiara Maura Ciniselli, Antonino Belfiore, Mara Lecchi, Enzo Masci, Gabriele Delconte, Massimo Primignani, Giulia Tosetti, Marco Dal Fante, Linda Fazzini, Aldo Airoldi, Marcello Vangeli, Francesca Turpini, Giovanni Giuseppe Rubis Passoni, Paolo Viaggi, Monica Arena, Roberta Ilaria Olimpia Motta, Anna Maria Cantù, Cristiano Crosta, Giuseppe De RobertoFrancesca Iannuzzi, Andrea Cassinotti, Valentina Dall'Olio, Laura Tizzoni, Gabriella Sozzi, Emanuele Meroni, Luigi Bisanti, Marco Alessandro Pierotti, Paolo Verderio, Manuela Gariboldi

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1164-1173
JournalInternational Journal of Cancer
Volume146
Issue number4
DOIs
Publication statusPublished - 2020

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Keywords

  • colorectal cancer
  • early diagnosis
  • miRNA
  • screening program

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zanutto, S., Ciniselli, C. M., Belfiore, A., Lecchi, M., Masci, E., Delconte, G., Primignani, M., Tosetti, G., Dal Fante, M., Fazzini, L., Airoldi, A., Vangeli, M., Turpini, F., Rubis Passoni, G. G., Viaggi, P., Arena, M., Motta, R. I. O., Cantù, A. M., Crosta, C., ... Gariboldi, M. (2020). Plasma miRNA-based signatures in CRC screening programs. International Journal of Cancer, 146(4), 1164-1173. https://doi.org/10.1002/ijc.32573