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

• Published in: PloS one 2019-01, Vol.14 (1), p.e0210400-e0210400
• Main Authors: Takashima, Yasuo, Kawaguchi, Atsushi, Iwadate, Yasuo, Hondoh, Hiroaki, Fukai, Junya, Kajiwara, Koji, Hayano, Azusa, Yamanaka, Ryuya
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Apoptosis; Biology and life sciences; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Cell migration; Central nervous system; Central Nervous System Neoplasms - drug therapy; Central Nervous System Neoplasms - genetics; Central Nervous System Neoplasms - pathology; Diagnosis; DNA microarrays; Dosage and administration; Drug therapy; Female; Follow-Up Studies; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genomes; Hodgkin's disease; Humans; Hybridization; Laboratories; Leukemia; Lymphoma; Lymphoma - drug therapy; Lymphoma - genetics; Lymphoma - pathology; Male; Medical prognosis; Medicine; Medicine and Health Sciences; Methotrexate; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Nervous system; Neurosurgery; Principal components analysis; Prognosis; Research and Analysis Methods; Ribonucleic acid; RNA; Smad protein; Stem cells; Survival; Survival Rate
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0210400

MicroRNAs (miRNAs) are small RNA molecules that inhibit gene function by suppressing translation of target genes. However, in primary central nervous system lymphoma (PCNSL), the biological significance of miRNAs is largely unknown, although some miRNAs are known to be prognosis markers. Here, we analyzed 847 miRNAs expressed in 27 PCNSL specimens using microarray profiling and surveyed miRNA signature for prognostic prediction. Of these, 16 miRNAs were expressed in 27 PCNSL specimens at a frequency of 48%. Their variable importance measured by Random forest model revealed miR-192, miR-486, miR-28, miR-52, miR-181b, miR-194, miR-197, miR-93, miR-708, and let-7g as having positive effects; miR-29b-2*, miR-126, and miR-182 as having negative effects; and miR-18a*, miR-425, and miR-30d as neutral. After principal component analysis, the prediction formula for prognosis, consisting of the expression values of the above-mentioned miRNAs, clearly divided Kaplan-Meier survival curves by the calculated Z-score (HR = 6.4566, P = 0.0067). The 16 miRNAs were enriched by gene ontology terms including angiogenesis, cell migration and proliferation, and apoptosis, in addition to signaling pathways including TGF-β/SMAD, Notch, TNF, and MAPKinase. Their target genes included BCL2-related genes, HMGA2 oncogene, and LIN28B cancer stem cell marker. Furthermore, three miRNAs including miR-181b, miR-30d, and miR-93, selected from the 16 miRNAs, also showed comparable results for survival (HR = 8.9342, P = 0.0007), suggestive of a miRNA signature for prognostic prediction in PCNSL. These results indicate that this miRNA signature is useful for prognostic prediction in PCNSL and would help us understand target pathways for therapies in PCNSL.