Abstract
BackgroundEpidemiological evidence links Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) to B-cell non-Hodgkin lymphoma (B-NHL). These B-NHLs, particularly those associated with HCV, may represent a distinct sub-group with peculiar molecular features, including peculiar expression of microRNAs (miRs).The aim of the present study was to search for miRs whose level in indolent B-NHL tissues could be associated with HBV or HCV infection.MethodsFourteen formalin fixed paraffin embedded (FFPE) tissues from HBV+, HCV+ and HBV-/HCV- indolent B-NHL patients were analyzed for levels of 34 selected miRs by quantitative Real-Time PCR. Reactive lymph nodes (RLNs) from HBV-/HCV- patients were included as non-tumor control. Statistical analysis of output data included Pearson and Spearman correlation and Mann-Whitney test and were carried out by the STATA software.ResultsMiR-92a was decreased exclusively in HBV-/HCV- B-NHLs, while miR-30b was increased in HBV+ and HCV+ samples, though only the HCV+ achieved full statistical significance. Analysis of a small subset of B-NHLs belonging to the same histological subtype (Nodal Marginal Zone Lymphoma) highlighted three miRs associated with HCV infection (miR-223, miR-29a and miR-29b) and confirmed decreased level of miR-92a in HBV-/HCV- samples also when considering this restricted B-NHL group.ConclusionsAlthough caution is needed due to the limited number of analyzed samples, overall the results suggest that differences at the miR expression level exist between indolent B-NHLs developed in patients with or without HBV or HCV infection. The identification of three further miRs associated with HCV by analyzing histologically homogeneous samples suggests that variations of miR levels possibly associated with HBV or HCV may be obscured by the tissue-specific variability of miR level associated with the different histological subtypes of B-NHL. Thus, the identification of further miRs will require, in addition to an increased sample size, the comparison of B-NHL tissues with the same histological classification.
Highlights
Epidemiological evidence links Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) to B-cell nonHodgkin lymphoma (B-NHL)
HCV-associated B-NHLs have been reported to be highly responsive to antiviral therapy: clearance of HCV resulted in remission of B-NHL, and reappearance of infection was associated with relapse of the disease
Conclusions the significance is hampered by the limited number of available samples, the present study suggests the existence of differences at the miR expression level between indolent B-NHLs developed in patients with or without HBV or HCV infection
Summary
Epidemiological evidence links Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) to B-cell nonHodgkin lymphoma (B-NHL) These B-NHLs, those associated with HCV, may represent a distinct subgroup with peculiar molecular features, including peculiar expression of microRNAs (miRs). Further support for HCV playing a role in development of lymphoma has come from reports on the treatment of HCV infection in B-NHL patients [9,10,11,12] In these studies, HCV-associated B-NHLs have been reported to be highly responsive to antiviral therapy: clearance of HCV resulted in remission of B-NHL, and reappearance of infection was associated with relapse of the disease. The mechanism(s) underlying the role of HCV in the pathogenesis of B-NHLs, as well as the associated molecular alterations, remain(s) to be clarified
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