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:	Ji Hye Im, Tae Hoon Kim, Kyue-Yim Lee, Ho-Shin Gwak, Weiwei Lin, Jong Bae Park, Jong Heon Kim, Byong Chul Yoo, Seong-Min Park, Ji-Woong Kwon, Sang Hoon Shin, Heon Yoo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	leptomeningeal metastasis cerebrospinal fluid microRNA microarray biomarker Medicine R
Acceso en línea:	https://doaj.org/article/9060a613b0544b76883e437b87308ecc
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spelling	oai:doaj.org-article:9060a613b0544b76883e437b87308ecc2021-11-11T17:31:22ZExploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses10.3390/jcm102148602077-0383https://doaj.org/article/9060a613b0544b76883e437b87308ecc2021-10-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/21/4860https://doaj.org/toc/2077-0383The 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 (<i>n</i> = 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 (<i>n</i> = 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.Ji Hye ImTae Hoon KimKyue-Yim LeeHo-Shin GwakWeiwei LinJong Bae ParkJong Heon KimByong Chul YooSeong-Min ParkJi-Woong KwonSang Hoon ShinHeon YooMDPI AGarticleleptomeningeal metastasiscerebrospinal fluidmicroRNAmicroarraybiomarkerMedicineRENJournal of Clinical Medicine, Vol 10, Iss 4860, p 4860 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	leptomeningeal metastasis cerebrospinal fluid microRNA microarray biomarker Medicine R
spellingShingle	leptomeningeal metastasis cerebrospinal fluid microRNA microarray biomarker Medicine R Ji Hye Im Tae Hoon Kim Kyue-Yim Lee Ho-Shin Gwak Weiwei Lin Jong Bae Park Jong Heon Kim Byong Chul Yoo Seong-Min Park Ji-Woong Kwon Sang Hoon Shin Heon Yoo Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses
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 (<i>n</i> = 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 (<i>n</i> = 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.
format	article
author	Ji Hye Im Tae Hoon Kim Kyue-Yim Lee Ho-Shin Gwak Weiwei Lin Jong Bae Park Jong Heon Kim Byong Chul Yoo Seong-Min Park Ji-Woong Kwon Sang Hoon Shin Heon Yoo
author_facet	Ji Hye Im Tae Hoon Kim Kyue-Yim Lee Ho-Shin Gwak Weiwei Lin Jong Bae Park Jong Heon Kim Byong Chul Yoo Seong-Min Park Ji-Woong Kwon Sang Hoon Shin Heon Yoo
author_sort	Ji Hye Im
title	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_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_sort	exploratory profiling of extracellular micrornas in cerebrospinal fluid comparing leptomeningeal metastasis with other central nervous system tumor statuses
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9060a613b0544b76883e437b87308ecc
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Exploratory Profiling of Extracellular MicroRNAs in Cerebrospinal Fluid Comparing Leptomeningeal Metastasis with Other Central Nervous System Tumor Statuses

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