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Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses

The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM pathogenesis bec...

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Autores principales: Im, Ji Hye, Kim, Tae Hoon, Lee, Kyue-Yim, Gwak, Ho-Shin, Lin, Weiwei, Park, Jong Bae, Kim, Jong Heon, Yoo, Byong Chul, Park, Seong-Min, Kwon, Ji-Woong, Shin, Sang Hoon, Yoo, Heon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584800/
https://www.ncbi.nlm.nih.gov/pubmed/34768379
http://dx.doi.org/10.3390/jcm10214860
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author Im, Ji Hye
Kim, Tae Hoon
Lee, Kyue-Yim
Gwak, Ho-Shin
Lin, Weiwei
Park, Jong Bae
Kim, Jong Heon
Yoo, Byong Chul
Park, Seong-Min
Kwon, Ji-Woong
Shin, Sang Hoon
Yoo, Heon
author_facet Im, Ji Hye
Kim, Tae Hoon
Lee, Kyue-Yim
Gwak, Ho-Shin
Lin, Weiwei
Park, Jong Bae
Kim, Jong Heon
Yoo, Byong Chul
Park, Seong-Min
Kwon, Ji-Woong
Shin, Sang Hoon
Yoo, Heon
author_sort Im, Ji Hye
collection PubMed
description The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM pathogenesis because they reflect the activity of disseminating cancer cells. We isolated CSF extracellular miRNAs from patients (n = 65) of different central nervous system tumor statuses, including cancer control, healthy control, LM, brain metastasis (BM), and primary brain tumor (BT) groups, and performed miRNA microarrays. In unsupervised clustering analyses, all LM and two BM samples showed unique profiles. Among 30 miRNAs identified for LM-specific biomarkers via a Prediction Analysis of Microarrays, miR-335-5p and miR-34b-3p were confirmed in both the discovery and validation samples (n = 23). Next, we performed a significance analysis of the microarray (SAM) to extract discriminative miRNA profiles of two selected CSF groups, with LM samples revealing a greater number of discriminative miRNAs than BM and BT samples compared to controls. Using SAM comparisons between LM and BM samples, we identified 30 upregulated and 6 downregulated LM miRNAs. To reduce bias from different primary cancers, we performed a subset analysis with primary non-small cell lung cancer, and 12 of 13 upregulated miRNAs in LM vs. BM belonged to the upregulated miRNAs in LM. We identified possible target genes and their biological processes that could be affected by LM discriminative miRNAs in NSCLC using the gene ontology database. In conclusion, we identified a unique extracellular miRNA profile in LM CSF that was different from BM, suggesting the use of miRNAs as LM biomarkers in studies of LM pathogenesis.
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spelling pubmed-85848002021-11-12 Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses Im, Ji Hye Kim, Tae Hoon Lee, Kyue-Yim Gwak, Ho-Shin Lin, Weiwei Park, Jong Bae Kim, Jong Heon Yoo, Byong Chul Park, Seong-Min Kwon, Ji-Woong Shin, Sang Hoon Yoo, Heon J Clin Med Article The diagnosis of leptomeningeal metastasis (LM) is often difficult due to the paucity of cancer cells in cerebrospinal fluid (CSF) and nonspecific findings on neuroimaging. Investigations of extracellular microRNAs (miRNAs) in CSF could be used for both the diagnosis and study of LM pathogenesis because they reflect the activity of disseminating cancer cells. We isolated CSF extracellular miRNAs from patients (n = 65) of different central nervous system tumor statuses, including cancer control, healthy control, LM, brain metastasis (BM), and primary brain tumor (BT) groups, and performed miRNA microarrays. In unsupervised clustering analyses, all LM and two BM samples showed unique profiles. Among 30 miRNAs identified for LM-specific biomarkers via a Prediction Analysis of Microarrays, miR-335-5p and miR-34b-3p were confirmed in both the discovery and validation samples (n = 23). Next, we performed a significance analysis of the microarray (SAM) to extract discriminative miRNA profiles of two selected CSF groups, with LM samples revealing a greater number of discriminative miRNAs than BM and BT samples compared to controls. Using SAM comparisons between LM and BM samples, we identified 30 upregulated and 6 downregulated LM miRNAs. To reduce bias from different primary cancers, we performed a subset analysis with primary non-small cell lung cancer, and 12 of 13 upregulated miRNAs in LM vs. BM belonged to the upregulated miRNAs in LM. We identified possible target genes and their biological processes that could be affected by LM discriminative miRNAs in NSCLC using the gene ontology database. In conclusion, we identified a unique extracellular miRNA profile in LM CSF that was different from BM, suggesting the use of miRNAs as LM biomarkers in studies of LM pathogenesis. MDPI 2021-10-22 /pmc/articles/PMC8584800/ /pubmed/34768379 http://dx.doi.org/10.3390/jcm10214860 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Im, Ji Hye
Kim, Tae Hoon
Lee, Kyue-Yim
Gwak, Ho-Shin
Lin, Weiwei
Park, Jong Bae
Kim, Jong Heon
Yoo, Byong Chul
Park, Seong-Min
Kwon, Ji-Woong
Shin, Sang Hoon
Yoo, Heon
Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title_full Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title_fullStr Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title_full_unstemmed Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title_short Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
title_sort exploratory profiling of extracellular micrornas in cerebrospinal fluid comparing leptomeningeal metastasis with other central nervous system tumor statuses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584800/
https://www.ncbi.nlm.nih.gov/pubmed/34768379
http://dx.doi.org/10.3390/jcm10214860
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