MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma.
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 an...
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doaj-f549c046e130414793d1c6d6be0ff2562021-07-21T04:32:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01141e021040010.1371/journal.pone.0210400MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma.Yasuo TakashimaAtsushi KawaguchiYasuo IwadateHiroaki HondohJunya FukaiKoji KajiwaraAzusa HayanoRyuya YamanakaMicroRNAs (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.https://doi.org/10.1371/journal.pone.0210400 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yasuo Takashima Atsushi Kawaguchi Yasuo Iwadate Hiroaki Hondoh Junya Fukai Koji Kajiwara Azusa Hayano Ryuya Yamanaka |
spellingShingle |
Yasuo Takashima Atsushi Kawaguchi Yasuo Iwadate Hiroaki Hondoh Junya Fukai Koji Kajiwara Azusa Hayano Ryuya Yamanaka MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. PLoS ONE |
author_facet |
Yasuo Takashima Atsushi Kawaguchi Yasuo Iwadate Hiroaki Hondoh Junya Fukai Koji Kajiwara Azusa Hayano Ryuya Yamanaka |
author_sort |
Yasuo Takashima |
title |
MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. |
title_short |
MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. |
title_full |
MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. |
title_fullStr |
MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. |
title_full_unstemmed |
MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma. |
title_sort |
microrna signature constituted of mir-30d, mir-93, and mir-181b is a promising prognostic marker in primary central nervous system lymphoma. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pone.0210400 |
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