MicroRNAs as predictors for CNS relapse of systemic diffuse large B-cell lymphoma

Abstract

Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology. In this study, we utilized miRNA multiplex reading of systemic newly diagnosed DLBCL samples obtained from patients with clinical risk factors for CNS involvement whose disease course was distinguished by the presence or absence of subsequent CNS relapse. The analysis detected two differentially expressed miRNAs, miR-20a and miR-30d, that predict for CNS involvement. Replication of these results in different samples was used for validation. We performed bioinformatics miRNA-target enrichment analysis to reveal a number of putative mechanisms for these miRNAs regulation of CNS relapse, including neuronal plasticity and WNT signaling pathway. Altogether, we show that the expression level of two miRNAs may have valuable information that may refine stratification for patients-at-risk for relapse with CNS involvement in DLBCL. Further larger scale studies are needed to shed light on the pathways involved in this disease.

MicroRNAs in ascending thoracic aortic aneurysms

“…The false discovery rate method was used to control multiple observations, and the adjusted P-value was used for further analysis. Fold-change difference were calculated for each comparison and the P-value was determined where P-value <0.05 was considered significant [28][29][30]. The miRNAs which showed significant expression level differences between BB and BA samples were selected for further investigation.…”

miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma

“…The upregulation of miR-30d is also found in Hodgkin lymphoma [48]. Besides, differentially expressed miR-30d is reported as a reliable biomarker candidate in CNS-DLBCL [49]. A previous study has reported the downregulation of let-7e in DLBCL compared to normal lymph nodes whereas the reduced expression of let-7g shows a good event-free survival [50].…”

MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma

“…Furthermore, the plasma level of miR-93 is associated with higher mortality in 25 patients with lymphoma [44], which suggests that they are reliable biomarker candidates. Differentially expressed miR-30d is also predicted for CNS-DLBCL [45]. Although the data is limited by the small sample size and there is less evidence for the above-mentioned function and signaling pathways at present, it would help us to better understand biological significances of the CNS signature of miRNAs in PCNSL.…”