Deregulation of microRNA expression in peripheral blood mononuclear cells from patients with HCV-related malignancies.
OBJECTIVE
Hepatocellular carcinoma is one of the major causes of death due to cancer worldwide, and its association with hepatitis C virus infection has been definitively established. Hepatitis C virus is also involved in the pathogenesis of non-Hodgkin's lymphoma. This is the only virus infecting humans that is able to induce two different malignancies. We analyzed the expression levels of a panel of microRNA in peripheral blood mononuclear cells of patients with hepatitis C virus-related malignancies in order to find a disease-associated deregulation and identify specific biomarkers.


METHODS
We tested peripheral blood mononuclear cells isolated from patients with hepatocellular carcinoma, non-Hodgkin's lymphoma, hepatitis C virus without malignancies and healthy subjects for a panel of microRNA selected on the basis of previous studies. MicroRNA expression was evaluated by real-time PCR.


RESULTS
Our results showed an upregulation of miRNA-21 and downregulation of miRNA-26b in hepatocellular carcinoma and non-Hodgkin's lymphoma patients compared to controls (p < 0.001). Deregulation of miRNA-16 and miRNA-155 was limited to lymphoma patients.


CONCLUSIONS
This study shows that some microRNAs are differently expressed in peripheral blood mononuclear cells from hepatitis C virus patients who develop hepatocellular carcinoma or lymphoma, while others share a common behavior. Thus, analysis of the expression of microRNAs could be a noninvasive marker of hepatitis C virus-related carcinogenesis. This analysis could be a suitable tool for identifying the existence of a malignancy and also discriminating between these two hepatitis C virus-related cancers.
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. alepilu80@libero.it.
Alessia
A
Piluso
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. laura.gragnani@unifi.it.
Laura
L
Gragnani
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. elisa.fognani@gmail.com.
Elisa
E
Fognani
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. elena.grandini2@unibo.it.
Elena
E
Grandini
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. monica.monti@unifi.it.
Monica
M
Monti
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. cristina.stasi@unifi.it.
Cristina
C
Stasi
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. elisabetta.loggi@unibo.it.
Elisabetta
E
Loggi
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. marzia.margotti2@unibo.it.
Marzia
M
Margotti
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. fabio.conti2@studio.unibo.it.
Fabio
F
Conti
Department of Medical and Surgical Sciences, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. pietro.andreone@unibo.it.
Pietro
P
Andreone
Department of Experimental and Clinical Medicine, Center for Systemic Manifestations of Hepatitis Viruses (MASVE), University of Florence, Largo Brambilla 3, 50134, Florence, Italy. a.zignego@dmi.unifi.it.
Anna Linda
AL
Zignego
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000032:analysis; D006526:Hepatitis C / Q000150:complications* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D035683:MicroRNAs; D012334:RNA, Neoplasm
Biomarker; Hepatitis C virus; Hepatocellular carcinoma; Non-Hodgkin’s lymphoma; microRNA