title: Low expression of microRNA-146b-5p and microRNA-320d predicts poor outcome of large B-cell lymphoma treated with cyclophosphamide, doxorubicin, vincristine, and prednisone.
abstract: 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.
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China; Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, PR China.
authors.forename: Peng Yan
authors.initials: PY
authors.lastname: Wu
authors.affiliation: Priority Research Centre for Cancer Research, University of Newcastle, Newcastle, New South Wales 2300, Australia; Melanoma Research Laboratory, University of Newcastle, Newcastle, New South Wales 2300, Australia; Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi 030013, PR China.
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: State Key Laboratory for Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital, Shanghai 200025, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Molecular Biology, Shanxi Cancer Hospital and Institute, Taiyuan, Shanxi 030013, PR China.
authors.forename: Xiang Yun
authors.initials: XY
authors.lastname: Guo
authors.affiliation: Department of Pathology, Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, PR China. Electronic address: jfenwang@qq.com.
authors.forename: Jin Fen
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010597:Pharmacogenetics; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D011379:Prognosis; D012189:Retrospective Studies; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: C542542:MIRN146 microRNA, human; C572916:MIRN320 microRNA, human; D035683:MicroRNAs; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: CHOP; Diffuse large B-cell lymphoma; MiR-146b-5p; MiR-320d; Outcome