Abstract
Background: Diffuse large B-cell lymphoma (DLBCL) used to be defined as germinal center B-like and non-germinal center B-like subtypes, associated with different prognoses, but the conventional classification does not meet the needs of clinical practice because of DLBCL heterogeneity, a problem that might be improved by selection of miRNAs as biomarkers.Methods: Twelve patients with DLBCLs were used to screen out the aberrant miRNA profile using miRNA microarray technology in two patient subtypes (six germinal center B-like and six non-germinal center B-like patients). The potential biomarkers were further analyzed using the quantitative reverse transcription-polymerase chain reaction method in 95 DLBCL patients to investigate relationships among expression levels of potent miRNA, clinicopathological features and survival rates of patients.Results: miR-208a-5p, miR-296-5p and miR-1304-5p were screened as potential biomarkers. miR-208a-5p and miR-296-5p were shown to be associated with better survival of patients after Kaplan–Meier analysis, whereas miR-1304-5p overexpression indicated a poor survival prognosis independent of the DLBCL subtype. In addition, changes of miR-296-5p and miR-1304-5p expression, the International Prognostic Index (IPI) status and the age of patients were all independent indicators for DLBCL prognosis. We also found that high miR-208a-5p expression led to better outcomes in DLBCL patients with similar IPI scores; however high miR-1304-5p expression tended to indicate the opposite.Conclusions: MiR-208a-5p, miR-296-5p and miR-1304-5p levels might be potential biomarkers for the prediction of the prognosis of DLBCL patients.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is recognized as one of the most prevalent subtypes of non-Hodgkin’s lymphoma [1], which can be further divided into two distinct subtypes, namely the germinal center B-like DLBCL (GCB-DLBCL) and the non-germinal center B-like subtype according to the Hans’ system [2,3]
The miRNA expression patterns from the 12 DLBCL specimens (6 GCB cases and 6 non-germinal center B-like subtype (non-GCB) cases) after microarray analysis revealed significant difference between GCB and non-GCB; in particular, the three most differentially expressed miRNAs were detected in DLBCL, which were miR-296-5p, miR-208a-5p and miR-1304-5p
Compared with non-GCB DLBCL cases, miR-296-5p and miR-208a-5p levels in GCB were significantly up-regulated, while miR-1304-5p was most highly expressed in non-GCB subtype cases as revealed by microarray analysis (Figure 2A)
Summary
Diffuse large B-cell lymphoma (DLBCL) is recognized as one of the most prevalent subtypes of non-Hodgkin’s lymphoma [1], which can be further divided into two distinct subtypes, namely the germinal center B-like DLBCL (GCB-DLBCL) and the non-germinal center B-like subtype (non-GCB) according to the Hans’ system [2,3]. The non-GCB phenotype is associated with substantially worse outcomes when treated with standard chemoimmunotherapy, whereas GCB has a better 5-year survival rate than for non-GCB subtype patients [1,2]. Diffuse large B-cell lymphoma (DLBCL) used to be defined as germinal center B-like and non-germinal center B-like subtypes, associated with different prognoses, but the conventional classification does not meet the needs of clinical practice because of DLBCL heterogeneity, a problem that might be improved by selection of miRNAs as biomarkers. The potential biomarkers were further analyzed using the quantitative reverse transcription-polymerase chain reaction method in 95 DLBCL patients to investigate relationships among expression levels of potent miRNA, clinicopathological features and survival rates of patients. MiR-208a-5p and miR-296-5p were shown to be associated with better survival of patients after Kaplan–Meier analysis, whereas miR-1304-5p overexpression indicated a poor survival prognosis independent of the DLBCL subtype. Conclusions: MiR-208a-5p, miR-296-5p and miR-1304-5p levels might be potential biomarkers for the prediction of the prognosis of DLBCL patients
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