Abstract
Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes; germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p < 0.05). Significantly higher miRNA-21 was detected in ABC sub-type compared to GCB sub-type (p = 0.00). Higher miRNA-21 was associated with worse response (p = 0.016), 2 years overall (p = 0.017) and progression free survival with statistical significance (p= 0.003). Significantly higher miRNA-21 levels were detected in HCV positive DLBCL patients compared to HCV negative patients (p = 0.00). Higher miRNA-21 levels were detected in HCV positive ABC subtype than GCB subtype (p = 0.05). Significantly higher levels were also detected in HCV positive controls compared to HCV negative controls. Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiRNA-21 is associated with poor response to treatment and survival in DLBCL. MiRNA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.
Highlights
MicroRNAs are small RNA molecules which control the expression of many target messenger RNAs involved in cell differentiation, proliferation and apoptosis
In summary our results suggest that miRNA-21 is a marker of diagnostic and prognostic relevance in diffuse large B-cell lymphoma (DLBCL), with its two molecular subtypes
MiRNA-21 was overexpressed in DLBCL patients with higher levels detected in activated B-cell-like (ABC) patients compared to germinal center B-cell (GCB) patients
Summary
MicroRNAs are small RNA molecules which control the expression of many target messenger RNAs involved in cell differentiation, proliferation and apoptosis Their aberrant expression is related to the pathogenesis of many human diseases such as infections, inflammatory disorders, immune diseases and cancers [1]. Higher miRNA-21 levels were detected in HCV positive DLBCL patients compared to HCV negative patients (p = 0.00). Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiRNA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients
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