Clinicopathologic implication of microRNA-197 in diffuse large B cell lymphoma

DC Field Value Language
dc.contributor.authorYang, Jeong Mi-
dc.contributor.authorJang, Ji-Young-
dc.contributor.authorJeon, Yoon Kyung-
dc.contributor.authorPaik, Jin Ho-
dc.identifier.citationJournal of Translational Medicine, 16(1):162ko_KR
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.

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.

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.

These results suggest the role of miR-197 as a biomarker with potential therapeutic implications.
dc.description.sponsorshipThis work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) of Korea funded by the Ministry of Education (NRF-2016R1D1A1B03935507) and a Grant (03-2011-015) from the Seoul National University Bundang Hospital Research Fund.ko_KR
dc.publisherBioMed Centralko_KR
dc.subjectDifuse large B cell lymphomako_KR
dc.titleClinicopathologic implication of microRNA-197 in diffuse large B cell lymphomako_KR
dc.rights.holderThe Author(s)-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
Files in This Item:
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.