Differential expression of miRNAs as biomarkers for predicting the outcomes of diffuse large B-cell lymphoma patients

Abstract

Background: Diffuse large B-cell lymphoma 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 diffuse large B-cell lymphoma heterogeneity, a problem that might be improved by selection of miRNAs as biomarkers. Methods: Twelve patients with diffuse large B-cell lymphomas were used to screen out the aberrant miRNA profile using miRNA microarray technology in 2 patient subtypes (6 germinal center B-like and 6 non-germinal center B-like patients). The potential biomarkers were further analyzed using the quantitative reverse transcription-polymerase chain reaction method in 95 diffuse large B-cell lymphoma patients to investigate relationships between 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 diffuse large B-cell lymphoma subtype. In addition, changes of miR-296-5p and miR-1304-5p expression, the International Prognostic Index status and the age of patients were all independent indicators for diffuse large B-cell lymphoma prognosis. We also found that high miR-208a-5p expression led to better outcomes in diffuse large B-cell lymphoma patients with similar International Prognostic Index 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 diffuse large B-cell lymphoma patients.

Implicación de la expresión condicional de HGAL en modelos murinos de linfoma de células grandes B difuso

“…Lo que sí se sabe es que la expresión de HGAL está estrictamente regulada y limitada al centro germinal 11,122,171 , viéndose activada por la acción de la IL-4 y de la IL-13 secretadas por el microambiente del propio centro germinal 144,148,185 y reprimida por la estimulación del BCR y CD40 142,143,166 . Asimismo, la expresión de PRDM1 159 y mir-155 211,[224][225][226] , que están implicados en la finalización de la reacción del centro germinal y la diferenciación en células plasmáticas, también reprimen la expresión de HGAL.…”