Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone

• Published in: Human pathology 2014-08, Vol.45 (8), p.1664-1673
• Main Authors: Wu, Peng Yan, BM, Zhang, Xu Dong, PhD, Zhu, Jiang, PhD, Guo, Xiang Yun, PhD, Wang, Jin Fen, MD
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Cancer; Cell growth; Cell Proliferation; CHOP; Confidence intervals; Cyclophosphamide - administration & dosage; Cyclophosphamide - therapeutic use; Diffuse large B-cell lymphoma; Disease-Free Survival; Doxorubicin - administration & dosage; Doxorubicin - therapeutic use; Gene expression; Genotype; Hematology; Humans; Hybridization; Lymphoma; Lymphoma, Large B-Cell, Diffuse - drug therapy; Lymphoma, Large B-Cell, Diffuse - genetics; Medical prognosis; MicroRNAs; MicroRNAs - genetics; Middle Aged; MiR-146b-5p; MiR-320d; Outcome; Pathology; Pharmacogenetics; Polymerase chain reaction; Prednisone - administration & dosage; Prednisone - therapeutic use; Prognosis; Retrospective Studies; Vincristine - administration & dosage; Vincristine - therapeutic use
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2014.04.002

Summary Although diffuse large B-cell lymphoma (DLBCL) encompasses a biologically and clinically diverse set of diseases, increasing evidence has pointed to an important role of microRNAs (miRs) in the pathogenesis of DLBCL. We report here that low expression of miR-146b-5p and miR-320d is associated with poor prognosis of DLBCL patients treated with the standard cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen and that this is related to the inhibitory effect of these miRs on DLBCL cell proliferation. Analysis of a retrospective cohort of 106 primary nodal DLBCL samples from patients who were treated with CHOP showed that, when the median survival period (40.8 months) was used as the cutoff point, miR-146b-5p and miR-320d were expressed at lower levels in DLBCLs with poor prognosis. Indeed, whereas low expression of miR-146b-5p was correlated with reduced progression-free survival, low expression of miR-320d was associated with decreases in both progression-free survival and overall survival. Moreover, miR-146b-5p and miR-320d were expressed at significantly lower levels in DLBCLs with the MYC t(8;14) translocation. Functional studies demonstrated that overexpression of miR-146b-5p or miR-320d inhibited DLBCL cell proliferation, wheareas knockdown of miR-146b-5p or miR-320d promoted proliferation of DLBCL cells. Taken together, these results suggest that low expression of miR-146b-5p and miR-320d may be predictive of compromised responses of a subset of DLBCL patients to treatment with the CHOP regimen and that restoration of these miRs may be useful to improve the therapeutic efficacy of CHOP.