Identification of microRNAs in the cerebrospinal fluid as marker for primary diffuse large B-cell lymphoma of the central nervous system

• Published in: Blood Vol. 117; no. 11; pp. 3140 - 3146
• Main Authors: Baraniskin, Alexander, Kuhnhenn, Jan, Schlegel, Uwe, Chan, Andrew, Deckert, Martina, Gold, Ralf, Maghnouj, Abdelouahid, Zöllner, Hannah, Reinacher-Schick, Anke, Schmiegel, Wolff, Hahn, Stephan A., Schroers, Roland
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 17.03.2011; Americain Society of Hematology
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers, Tumor - cerebrospinal fluid; Biomarkers, Tumor - genetics; Case-Control Studies; Central Nervous System Neoplasms - cerebrospinal fluid; Central Nervous System Neoplasms - diagnosis; Central Nervous System Neoplasms - genetics; Female; Gene Expression Regulation, Leukemic; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Large B-Cell, Diffuse - cerebrospinal fluid; Lymphoma, Large B-Cell, Diffuse - diagnosis; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Medical sciences; MicroRNAs - cerebrospinal fluid; MicroRNAs - genetics; Middle Aged; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; RNA Stability - genetics; ROC Curve; RNA interference; Hematology; Micro RNA; Central nervous system; Biological marker; B cell neoplasm; Malignant hemopathy; Cerebrospinal fluid; Non Hodgkin lymphoma; Gene silencing; Lymphoproliferative syndrome; Primary; Diffuse large B cell lymphoma; Cancer
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2010-09-308684

The diagnosis of primary central nervous system lymphoma (PCNSL) depends on histopathology of brain biopsies, because disease markers in the cerebrospinal fluid (CSF) with sufficient diagnostic accuracy are not available yet. MicroRNAs (miRNAs) are regulatory RNA molecules that are deregulated in many disease types, including cancer. Recently, miRNAs have shown promise as markers for cancer diagnosis. In this study, we demonstrate that miRNAs are present in the CSF of patients with PCNSL. With a candidate approach and miRNA quantification by reverse transcription polymerase chain reaction, miRNAs with significant levels in the CSF of patients with PCNSL were identified. MiR-21, miR-19, and miR-92a levels in CSF collected from patients with PCNSL and from controls with inflammatory CNS disorders and other neurologic disorders indicated a significant diagnostic value of this method. Receiver-operating characteristic analyses showed area under the curves of 0.94, 0.98, and 0.97, respectively, for miR-21, miR-19, and miR-92a CSF levels in discriminating PCNSL from controls. More importantly, combined miRNA analyses resulted in an increased diagnostic accuracy with 95.7% sensitivity and 96.7% specificity. We also demonstrated a remarkable stability of miRNAs in the CSF. In conclusion, CSF miRNAs are potentially useful tools as novel noninvasive biomarker for the diagnosis of PCNSL.