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

1 Citation (Scopus)

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
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

MicroRNAs
Early Detection of Cancer
Adenoma
Colorectal Neoplasms
Colonoscopy
Neoplasms
Workflow
Tumor Biomarkers
ROC Curve
Real-Time Polymerase Chain Reaction
Appointments and Schedules
Multivariate Analysis
Confidence Intervals
Mortality

Keywords

  • colorectal cancer
  • early diagnosis
  • miRNA
  • screening program

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Plasma miRNA-based signatures in CRC screening programs. / 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.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Zanutto, S, Ciniselli, CM, 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, GG, Viaggi, P, Arena, M, Motta, RIO, Cantù, AM, Crosta, C, De Roberto, G, Iannuzzi, F, Cassinotti, A, Dall'Olio, V, Tizzoni, L, Sozzi, G, Meroni, E, Bisanti, L, Pierotti, MA, Verderio, P & Gariboldi, M 2019, 'Plasma miRNA-based signatures in CRC screening programs', International Journal of Cancer. https://doi.org/10.1002/ijc.32573
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. / Plasma miRNA-based signatures in CRC screening programs. In: International Journal of Cancer. 2019.
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AU - Masci, Enzo

AU - Delconte, Gabriele

AU - Primignani, Massimo

AU - Tosetti, Giulia

AU - Dal Fante, Marco

AU - Fazzini, Linda

AU - Airoldi, Aldo

AU - Vangeli, Marcello

AU - Turpini, Francesca

AU - Rubis Passoni, Giovanni Giuseppe

AU - Viaggi, Paolo

AU - Arena, Monica

AU - Motta, Roberta Ilaria Olimpia

AU - Cantù, Anna Maria

AU - Crosta, Cristiano

AU - De Roberto, Giuseppe

AU - Iannuzzi, Francesca

AU - Cassinotti, Andrea

AU - Dall'Olio, Valentina

AU - Tizzoni, Laura

AU - Sozzi, Gabriella

AU - Meroni, Emanuele

AU - Bisanti, Luigi

AU - Pierotti, Marco Alessandro

AU - Verderio, Paolo

AU - Gariboldi, Manuela

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