Abstract

The diagnosis of primary central nervous system (CNS) lymphoma, which is predominantly of the diffuse large B-cell lymphoma type (CNS DLBCL), is challenging. MicroRNAs (miRs) are gene expression-regulating non-coding RNAs that are potential biomarkers. We aimed to distinguish miR expression patterns differentiating CNS DLBCL and non-malignant CNS diseases with tumor presentation (n-ML). Next generation sequencing-based miR profiling of cerebrospinal fluids (CSFs) and brain tumors was performed. Sample source-specific (CSF vs. brain tumor) miR patterns were revealed. Even so, a set of 17 miRs differentiating CNS DLBCL from n-ML, no matter if assessed in CSF or in a tumor, was identified. Along with the results of pathway analyses, this suggests their pathogenic role in CNS DLBCL. A combination of just four of those miRs (miR-16-5p, miR-21-5p, miR-92a-3p, and miR-423-5p), assessed in CSFs, discriminated CNS DLBCL from n-ML samples with 100% specificity and 67.0% sensitivity. Analyses of paired CSF-tumor samples from patients with CNS DLBCL showed significantly lower CSF levels of miR-26a, and higher CSF levels of miR-15a-5p, miR-15b-5p, miR-19a-3p, miR-106b-3p, miR-221-3p, and miR-423-5p. Noteworthy, the same miRs belonged to the abovementioned set differentiating CNS DLBCL from non-malignant CNS diseases. Our results not only add to the basic knowledge, but also hold significant translational potential.

Highlights

  • Primary central nervous system (CNS) lymphoma (PCNSL) is a malignant extranodal form of aggressive B-cell non-Hodgkin lymphoma (B-NHL), predominantly of the histological subtype of primary diffuse large B-cell lymphoma (CNS DLBCL)

  • We demonstrated that CNS DLBCL cerebrospinal fluids (CSFs) and the relevant brain biopsy samples are characterized by specific, different miR profiles [13]

  • In line with our previous RTq-PCR-based study that focused on seven miRs [13], we revealed CNS DLBCL-specific miR profiles that are different for CSF and brain biopsy samples

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Summary

Introduction

Primary central nervous system (CNS) lymphoma (PCNSL) is a malignant extranodal form of aggressive B-cell non-Hodgkin lymphoma (B-NHL), predominantly of the histological subtype of primary diffuse large B-cell lymphoma (CNS DLBCL). PCNSL shares some clinical symptoms with a number of non-neoplastic neurological disorders, and in imaging exams, inflammatory and other non-neoplastic lesions often present as tumors 4.0/). Biomolecules 2021, 11, 1395 resembling PCNSL [1,2,3]. Cases with unspecific presentations of brain disorders qualify for time-consuming enhanced diagnostics, while they often require acute treatment (e.g., due to cerebral edema). Examination of brain biopsy material [3]. The invasive procedure of stereotactic brain biopsy carries a risk of major complications, including intracranial hemorrhage. Stereotactic brain biopsy cannot be performed due to the inaccessible location of the lesion; in many cases, because of a common initial steroid therapy resulting in vanishing tumors, HP/IHC examination of brain biopsy samples are inconclusive [4,5]

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