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

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-197^low and non-GCB/miR-197^high groups, progression was most frequently observed in the non-GCB/miR-197^low 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.

SUBMITTER: Yang JM 

PROVIDER: S-EPMC5996506 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature