Abstract
The performance of circulating biomarkers for the diagnosis of hepatocellular carcinoma (HCC) is sub-optimal. In this study we tested circulating microRNAs as biomarkers for HCC in cirrhotic patients by performing a two stage study: a discovery phase conducted by microarray and a validation phase performed by qRT-PCR in an independent series of 118 patients. Beside miRNAs emerged from the discovery phase, miR-21, miR-221, miR-519d were also tested in the validation setting on the basis of literary and tissue findings. Deregulated microRNAs were assayed in HCC-derived cells in the intracellular compartment, cell culture supernatant and exosomal fraction. Serum and tissue microRNA levels were compared in 14 patients surgically treated for HCC. From the discovery study, it emerged that seven circulating microRNAs were differentially expressed in cirrhotic patients with and without HCC. In the validation set, miR-939, miR-595 and miR-519d were shown to differentiate cirrhotic patients with and without HCC. MiR-939 and miR-595 are independent factors for HCC. ROC curves of miR-939, miR-595 and miR-519d displayed that AUC was higher than AFP. An exosomal secretion of miR-519d, miR-21, miR-221 and miR-1228 and a correlation between circulating and tissue levels of miR-519d, miR-494 and miR-21 were found in HCC patients. Therefore, we show that circulating microRNAs deserve attention as non-invasive biomarkers in the diagnostic setting of HCC and that exosomal secretion contributes to discharging a subset of microRNAs into the extracellular compartment.
Highlights
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, with an increasing incidence observed over the last decades [1]
A total of 122 miRNAs were detected in the serum of 23 patients (11 patients with liver cirrhosis and 12 patients with liver cirrhosis complicated by HCC)
HCC diagnostic and prognostic assessment represents a suitable setting to test circulating miRNAs performance due to: (1) the presence of a high risk population under surveillance, (2) the lack of reliable circulating biomarkers, (3) the possible difficulties in obtaining bioptic samples in cirrhotic patients with liver nodules of uncertain malignant potential identified with imaging techniques, (4) the prognostic impact of early diagnosis of HCC
Summary
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, with an increasing incidence observed over the last decades [1]. Diagnosing HCC in its early stages may strongly. Circulating microRNAs in Cirrhotic Patients with HCC. Bologna e Ravenna, to LB, GFS and LG; Italian Ministry of University and Research – PRIN 20102011 to LB; Italian Association for Cancer Research (AIRC) to MN and MF; Programma di Ricerca Regione-Università 2010-2012, Regione EmiliaRomagna, Bando "Alessandro Liberati", to FF, "Identification of innovative microRNAs-based biomarkers and anti-cancer strategies for the treatment of Hepatocellular carcinoma”
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
