Clinicopathologic implication of microRNA-197 in diffuse large B cell lymphoma.
J Transl Med
; 16(1): 162, 2018 06 11.
Article
em En
| MEDLINE
| ID: mdl-29890998
ABSTRACT
BACKGROUND:
Diffuse large B cell lymphoma (DLBCL) contains heterogeneous subtypes with various molecular dysregulation at the gene, protein and microRNA levels. Compared with the GCB subtype, the non-germinal center B-like (non-GCB)/activated B cell-like (ABC) subtype exhibits frequent progression despite standard immunochemotherapy. We aimed to investigate the effects of miR-197 on the progression and chemosensitivity of DLBCL with respect to the GCB and non-GCB/ABC subtypes.METHODS:
To screen distinctively expressed microRNAs, microRNA expression patterns were analyzed in 10 DLBCL cases by microarray chip assays. Using quantitative real-time polymerase chain reaction (qRT-PCR), associations between miR-197 expression levels and clinicopathologic variables were investigated in 51 DLBCL tissue samples. The effects of miR-197 on doxorubicin chemosensitivity were investigated using the OCI-Ly1 and SUDHL9 cell lines.RESULTS:
MicroRNA expression profiling by hierarchical clustering revealed that miR-197 was one of the distinctively expressed microRNAs in DLBCL. Quantitative analysis using qRT-PCR revealed that miR-197 levels were not correlated with clinicopathologic variables, including the international prognostic index, but low miR-197 levels were significantly associated with lymphoma progression defined by refractoriness, relapse or death in the rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-treated subgroup (n = 43; p = 0.004). Among the three molecular groups, i.e., the GCB, non-GCB/miR-197low and non-GCB/miR-197high groups, progression was most frequently observed in the non-GCB/miR-197low group in the full cohort (p = 0.013) and the R-CHOP cohort (p = 0.008). In survival analysis, low miR-197 levels were independently predictive of shorter progression-free survival in the R-CHOP cohort (p = 0.031; HR = 27.9) and the non-GCB subgroup (p = 0.037; HR = 21.5) but not in the GCB subgroup. Using SUDHL9 (ABC type) and OCI-Ly1 (GCB type) cells, the effects of doxorubicin on reducing cell viability were enhanced by miR-197 transfection. In apoptosis assays, miR-197 transfection enhanced doxorubicin-induced apoptosis in SUDHL9 cells but not in OCI-Ly1 cells, suggesting a chemosensitizing effect of miR-197 in ABC DLBCL.CONCLUSIONS:
These results suggest the role of miR-197 as a biomarker with potential therapeutic implications.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfoma Difuso de Grandes Células B
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MicroRNAs
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Transl Med
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Coréia do Sul