Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma

Farzaneh Moshiri, Alessandro Salvi, Laura Gramantieri, Angelo Sangiovanni, Paola Guerriero, Giuseppina De Petro, Cristian Bassi, Laura Lupini, Arash Sattari, Douglas Cheung, Dario Veneziano, Giovanni Nigita, Ram C. Shankaraiah, Nazario Portolani, Paolo Carcoforo, Francesca Fornari, Luigi Bolondi, Antonio Frassoldati, Silvia Sabbioni, Massimo ColomboCarlo M. Croce, Massimo Negrini

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma (HCC) is the most common liver cancer and second leading cause of cancer related death worldwide. Most HCCs occur in a damaged cirrhotic background and it may be difficult to discriminate between regenerative nodules and early HCCs. No dependable molecular biomarker exists for the early detection of HCC. MicroRNAs (miRNAs) have attracted attention as potential bloodbased biomarkers. To identify circulating miRNAs with diagnostic potential in HCC, we performed preliminary RNAseq studies on plasma samples from a small set of HCC patients, cirrhotic patients and healthy controls. Then, out of the identified miRNAs, we investigated miR-101-3p, miR-106b-3p, miR-1246 and miR-411-5p in plasma of independent HCC patients' cohorts. The use of droplet digital PCR (ddPCR) confirmed the aberrant levels of these miRNAs. The diagnostic performances of each miRNA and their combinations were measured using Receiver Operating Characteristic (ROC) curve analyses: a classifier consisting of miR-101-3p, miR-1246 and miR-106b- 3p produced the best diagnostic precision in plasma of HCC vs. cirrhotic patients (AUC = 0.99). A similar performance was found when the levels of miRNAs of HCC patients were compared to healthy controls (AUC = 1.00). We extended the analyses of the same miRNAs to serum samples. In serum of HCC vs. cirrhotic patients, the combination of miR-101-3p and miR-106b-3p exhibited the best diagnostic accuracy with an AUC = 0.96. Thus, circulating miR-101-3p, miR-106b-3p and miR-1246, either individually or in combination, exhibit a considerable potential value as diagnostic biomarkers of HCC.

Original languageEnglish
Pages (from-to)15350-15364
Number of pages15
JournalOncotarget
Volume9
Issue number20
DOIs
Publication statusPublished - Jan 1 2018

Keywords

  • Circulating microRNA
  • Cirrhosis
  • Diagnostic biomarkers
  • Hepatocellular carcinoma

ASJC Scopus subject areas

  • Oncology

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    Moshiri, F., Salvi, A., Gramantieri, L., Sangiovanni, A., Guerriero, P., De Petro, G., Bassi, C., Lupini, L., Sattari, A., Cheung, D., Veneziano, D., Nigita, G., Shankaraiah, R. C., Portolani, N., Carcoforo, P., Fornari, F., Bolondi, L., Frassoldati, A., Sabbioni, S., ... Negrini, M. (2018). Circulating miR-106b-3p, miR-101-3p and miR-1246 as diagnostic biomarkers of hepatocellular carcinoma. Oncotarget, 9(20), 15350-15364. https://doi.org/10.18632/oncotarget.24601