Plasma miRNA-based signatures in CRC screening programs: International Journal of Cancer

S. Zanutto, C.M. Ciniselli, A. Belfiore, M. Lecchi, E. Masci, G. Delconte, M. Primignani, G. Tosetti, M. Dal Fante, L. Fazzini, A. Airoldi, M. Vangeli, F. Turpini, G.G. Rubis Passoni, P. Viaggi, M. Arena, R.I.O. Motta, A.M. Cantù, C. Crosta, G. De RobertoF. Iannuzzi, A. Cassinotti, V. Dall'Olio, L. Tizzoni, G. Sozzi, E. Meroni, L. Bisanti, M.A. Pierotti, P. Verderio, M. Gariboldi

Research output: Contribution to journalArticlepeer-review


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. © 2019 UICC
Original languageEnglish
Pages (from-to)1164-1173
Number of pages10
JournalInt. J. Cancer
Issue number4
Publication statusPublished - 2020


  • colorectal cancer
  • early diagnosis
  • miRNA
  • screening program
  • microRNA
  • microRNA 106b 5p
  • microRNA 186 5p
  • microRNA 193a 5p
  • microRNA 218 5p
  • microRNA 320a 3p
  • microRNA 323a 3p
  • microRNA 324 3p
  • microRNA 331 3p
  • microRNA 335 5p
  • microRNA 342 3p
  • microRNA 423 5p
  • microRNA 483 5p
  • microRNA 532 3p
  • unclassified drug
  • adult
  • age distribution
  • aged
  • Article
  • blood level
  • blood sampling
  • cancer diagnosis
  • cancer grading
  • cancer screening
  • colon adenoma
  • colonoscopy
  • female
  • health program
  • human
  • major clinical study
  • male
  • multicenter study
  • priority journal
  • prospective study
  • quantitative analysis
  • real time polymerase chain reaction
  • sex difference
  • validation study
  • blood
  • colorectal tumor
  • early cancer diagnosis
  • genetics
  • middle aged
  • Aged
  • Colorectal Neoplasms
  • Early Detection of Cancer
  • Female
  • Humans
  • Male
  • MicroRNAs
  • Middle Aged

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