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Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers
This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML. BM aspirates were collected fr...
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Published in: | PloS one 2024-08, Vol.19 (8), p.e0306962 |
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description | This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML.
BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples.
We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers.
Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach. |
doi_str_mv | 10.1371/journal.pone.0306962 |
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BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples.
We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers.
Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0306962</identifier><identifier>PMID: 39178208</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acute myeloid leukemia ; Adult ; Aged ; Antibodies ; Biological markers ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Bone marrow ; Cancer ; Cell organelles ; Chromatography ; Correlation ; Extracellular vesicles ; Extracellular Vesicles - genetics ; Extracellular Vesicles - metabolism ; Female ; Gene expression ; Gene Expression Profiling ; Genomes ; Health aspects ; Humans ; Leukemia ; Leukemia, Myeloid, Acute - diagnosis ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - pathology ; Male ; Measurement ; Medical prognosis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Molecular weight ; mRNA ; Network analysis ; Oncology, Experimental ; Pathogenesis ; Patients ; Plasma ; Prognosis ; Proteins ; Ribonucleic acid ; Risk groups ; RNA ; Size exclusion chromatography ; Software ; Survival</subject><ispartof>PloS one, 2024-08, Vol.19 (8), p.e0306962</ispartof><rights>Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0003-1462-0502 ; 0000-0001-7292-2520 ; 0000-0001-7909-6639</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/3096537611/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3096537611?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,25753,27924,27925,37012,37013,44590,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39178208$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kang, Ka-Won</creatorcontrib><creatorcontrib>Gim, Jeong-An</creatorcontrib><creatorcontrib>Hong, Sunghoi</creatorcontrib><creatorcontrib>Kim, Hyun Koo</creatorcontrib><creatorcontrib>Choi, Yeonho</creatorcontrib><creatorcontrib>Park, Ji-Ho</creatorcontrib><creatorcontrib>Park, Yong</creatorcontrib><title>Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML.
BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples.
We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers.
Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.</description><subject>Acute myeloid leukemia</subject><subject>Adult</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Bone marrow</subject><subject>Cancer</subject><subject>Cell organelles</subject><subject>Chromatography</subject><subject>Correlation</subject><subject>Extracellular vesicles</subject><subject>Extracellular Vesicles - genetics</subject><subject>Extracellular Vesicles - metabolism</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - diagnosis</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Male</subject><subject>Measurement</subject><subject>Medical prognosis</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>Middle Aged</subject><subject>miRNA</subject><subject>Molecular weight</subject><subject>mRNA</subject><subject>Network analysis</subject><subject>Oncology, Experimental</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Plasma</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Ribonucleic acid</subject><subject>Risk groups</subject><subject>RNA</subject><subject>Size exclusion chromatography</subject><subject>Software</subject><subject>Survival</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNqNkttu1DAQhiMEogd4AwSWkBBc7OJD4iSXq4rDShWVCuU2cuzxrrdOnNpOaS95cxwaUBf1AtmSLeubf8Yzf5a9IHhJWEne79zoe2GXg-thiRnmNaePskNSM7rgFLPH9-4H2VEIO4wLVnH-NDtgNSkriqvD7OdFAOQ0gpvohQRrRys8uoZgpAXUGend-ZcVGrzTxkJApkeDiAb6GNAPE7dIyDEm8BasMwpZGC-hMwJp51HcAjIqoUYbmYJcP2Xq3TVY1BrXCX8JPjzLnmhhAzyfz-Ps4uOHbyefF6dnn9Ynq9OFyksSFzlVLeSa4BaAVVrSChNaccxIKwFTrSqiRK651rrgsiVlSetSlSL9sm2BADvOXt3pDtaFZu5eaBiuecFKTkgi1neEcmLXDN6kCm8bJ0zz-8H5TSN8nBrTtIXOWwxKck1zWtY1r4oibaILAUzKpPV2zubd1QghNp0JU39FD26c0xZViVlCX_-DPlzcTG1Eym967aaBTaLNqsJJiWFSJGr5AJWWSlORySnTFPcD3u0FJCYmL2zEGEKz_nr-_-zZ9332zT12C8LGbXB2nFwQ9sGX8-_HtgP1t-1_LMp-AVGm50o</recordid><startdate>20240823</startdate><enddate>20240823</enddate><creator>Kang, Ka-Won</creator><creator>Gim, Jeong-An</creator><creator>Hong, Sunghoi</creator><creator>Kim, Hyun Koo</creator><creator>Choi, Yeonho</creator><creator>Park, Ji-Ho</creator><creator>Park, Yong</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-1462-0502</orcidid><orcidid>https://orcid.org/0000-0001-7292-2520</orcidid><orcidid>https://orcid.org/0000-0001-7909-6639</orcidid></search><sort><creationdate>20240823</creationdate><title>Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers</title><author>Kang, Ka-Won ; Gim, Jeong-An ; Hong, Sunghoi ; Kim, Hyun Koo ; Choi, Yeonho ; Park, Ji-Ho ; Park, Yong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-d471t-42dbe4f10bee38fc2801286031bce02fd81da4f6fff56cb177297d7a208bbe1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acute myeloid leukemia</topic><topic>Adult</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Bone marrow</topic><topic>Cancer</topic><topic>Cell organelles</topic><topic>Chromatography</topic><topic>Correlation</topic><topic>Extracellular vesicles</topic><topic>Extracellular Vesicles - genetics</topic><topic>Extracellular Vesicles - metabolism</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genomes</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - diagnosis</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Male</topic><topic>Measurement</topic><topic>Medical prognosis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Middle Aged</topic><topic>miRNA</topic><topic>Molecular weight</topic><topic>mRNA</topic><topic>Network analysis</topic><topic>Oncology, Experimental</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Plasma</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Ribonucleic acid</topic><topic>Risk groups</topic><topic>RNA</topic><topic>Size exclusion chromatography</topic><topic>Software</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kang, Ka-Won</creatorcontrib><creatorcontrib>Gim, Jeong-An</creatorcontrib><creatorcontrib>Hong, Sunghoi</creatorcontrib><creatorcontrib>Kim, Hyun Koo</creatorcontrib><creatorcontrib>Choi, Yeonho</creatorcontrib><creatorcontrib>Park, Ji-Ho</creatorcontrib><creatorcontrib>Park, Yong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>Advanced Technologies & Aerospace Database (1962 - 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Academic</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kang, Ka-Won</au><au>Gim, Jeong-An</au><au>Hong, Sunghoi</au><au>Kim, Hyun Koo</au><au>Choi, Yeonho</au><au>Park, Ji-Ho</au><au>Park, Yong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-08-23</date><risdate>2024</risdate><volume>19</volume><issue>8</issue><spage>e0306962</spage><pages>e0306962-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>This study aimed to establish clinically significant microRNA (miRNA) sets using extracellular vesicles (EVs) from bone marrow (BM) aspirates of patients with acute myelogenous leukemia (AML), and to identify the genes that interact with these EV-derived miRNAs in AML.
BM aspirates were collected from 32 patients with AML at the time of AML diagnosis. EVs were isolated using size-exclusion chromatography. A total of 965 EV-derived miRNAs were identified in all the samples.
We analyzed the expression levels of these EV-derived miRNAs of the favorable (n = 10) and non-favorable (n = 22) risk groups; we identified 32 differentially expressed EV-derived miRNAs in the non-favorable risk group. The correlation of these miRNAs with risk stratification and patient survival was analyzed using the information of patients with AML from The Cancer Genome Atlas (TCGA) database. Of the miRNAs with downregulated expression in the non-favorable risk group, hsa-miR-181b and hsa-miR-143 were correlated with non-favorable risk and short overall survival. Regarding the miRNAs with upregulated expression in the non-favorable risk group, hsa-miR-188 and hsa-miR-501 were correlated with non-favorable risk and could predict poor survival. Through EV-derived miRNAs-mRNA network analysis using TCGA database, we identified 21 mRNAs that could be potential poor prognosis biomarkers.
Overall, our findings revealed that EV-derived miRNAs can serve as biomarkers for risk stratification and prognosis in AML. In addition, these EV-derived miRNA-based bioinformatic analyses could help efficiently identify mRNAs with biomarker potential, similar to the previous cell-based approach.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39178208</pmid><doi>10.1371/journal.pone.0306962</doi><tpages>e0306962</tpages><orcidid>https://orcid.org/0000-0003-1462-0502</orcidid><orcidid>https://orcid.org/0000-0001-7292-2520</orcidid><orcidid>https://orcid.org/0000-0001-7909-6639</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Acute myeloid leukemia Adult Aged Antibodies Biological markers Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Bone marrow Cancer Cell organelles Chromatography Correlation Extracellular vesicles Extracellular Vesicles - genetics Extracellular Vesicles - metabolism Female Gene expression Gene Expression Profiling Genomes Health aspects Humans Leukemia Leukemia, Myeloid, Acute - diagnosis Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Male Measurement Medical prognosis MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism Middle Aged miRNA Molecular weight mRNA Network analysis Oncology, Experimental Pathogenesis Patients Plasma Prognosis Proteins Ribonucleic acid Risk groups RNA Size exclusion chromatography Software Survival |
title | Use of extracellular vesicle microRNA profiles in patients with acute myeloid leukemia for the identification of novel biomarkers |
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