Expression Signature of MicroRNA-155 and its Association with Response to Treatment within Different Subtypes of B-Cell Malignancies

Abstract

Objectives: Emerging evidence suggests that microRNAs could serve as non-invasive biomarkers for cancer patients. However, they are mostly not fully investigated as biomarkers in the classification, progression and prognosis of different cancers. Our study was designed to explore the microRNA-155 (miR-155) expression levels in peripheral blood mononuclear cells (PBMCs) in patients with various subtypes of B-cell malignancies. Also, we aimed to correlate between miR-155 expression levels and the diverse clinico-pathologic features as well as the prognostic fate of these patients after treatment completion. Subjects and methods:Using whole blood samples from 53 patients with B-cell malignancies and 15 apparently healthy subjects, miR-155 was extracted and profiled by quantitative real-time PCR (RT-qPCR). The B-cell malignancies patients were including 22 diffuse large B-cell lymphoma (DLBCL), 15 chronic lymphocytic leukemia (CLL), 9 follicular lymphoma patients (FL) and 7 subjects with burkitt′s lymphoma (BL). The samples were withdrawn before starting chemotherapy in addition to after completing their therapeutic courses by 6 months. Subsequently, the patients were further sub-grouped into those with partial remission, complete remission, resistant disease and relapse. Results:We found that miR-155 expression levels differentiate lymphoma entities from normal subjects (p ≤ 0.001) and its expression fold changes distinguish B-cell lymphoma subtypes from each other's (p<0.05). In addition, miR-155 was significantly correlated with age and LDH levels. The receiver operating curve (ROC) was employed to identify the diagnostic outcomes of miR-155 in discriminating B-cell malignancies entities from each other's (AUC=0.957 for DLBCL vs. CLL+FL and AUC=1.000 for CLL vs. FL). Otherwise, when BL was versus healthy controls the AUC was equal to 0.552. As well, we demonstrated an association between elevated miR-155 expression levels and poor response to treatment with increased cases of relapse, partial remission or resistance to treatment. Conclusions:This study suggests that miR-155 has an expression profile that differs according to B-cell malignancies subtype. Besides, miR-155 expression levels may modulate the patient's response to treatment. These results support a role for miR-155 to provide helpful diagnostic/prognostic information in B-cell malignancies and may highlight novel pathways to be targeted for therapeutics in the future.