Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer
Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible...
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| creator | Schee, Kristina Lorenz, Susanne Worren, Merete Molton Günther, Clara-Cecilie Holden, Marit Hovig, Eivind Fodstad, Oystein Meza-Zepeda, Leonardo A Flatmark, Kjersti |
| description | Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC. |
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MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0066165</identifier><identifier>PMID: 23824282</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adenomatous polyposis coli ; Analysis ; Biology ; Biomarkers ; Biomarkers, Tumor - genetics ; Cancer ; Cancer metastasis ; Cluster Analysis ; Colon ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Dihydrofolate reductase ; Female ; Gene expression ; Gene sequencing ; Genes ; Genomics ; Hazard identification ; Health aspects ; High-Throughput Nucleotide Sequencing - methods ; Hospitals ; Humans ; Informatics ; Male ; Medical prognosis ; Medical research ; Medicine ; Metastases ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; miRNA ; Non-coding RNA ; Patients ; Prognosis ; Proportional Hazards Models ; Real-Time Polymerase Chain Reaction ; Rectum ; Ribonucleic acid ; RNA ; Statistical models ; Studies ; Surgery ; Transcriptome ; Tumors</subject><ispartof>PloS one, 2013-06, Vol.8 (6), p.e66165-e66165</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Schee et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>2013 Schee et al 2013 Schee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-b8237e7dcb3e1cb3d58d183340d6816c77a26448e54328db6c399d5c23d9b69e3</citedby><cites>FETCH-LOGICAL-c758t-b8237e7dcb3e1cb3d58d183340d6816c77a26448e54328db6c399d5c23d9b69e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688869/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3688869/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23824282$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hold, Georgina L.</contributor><creatorcontrib>Schee, Kristina</creatorcontrib><creatorcontrib>Lorenz, Susanne</creatorcontrib><creatorcontrib>Worren, Merete Molton</creatorcontrib><creatorcontrib>Günther, Clara-Cecilie</creatorcontrib><creatorcontrib>Holden, Marit</creatorcontrib><creatorcontrib>Hovig, Eivind</creatorcontrib><creatorcontrib>Fodstad, Oystein</creatorcontrib><creatorcontrib>Meza-Zepeda, Leonardo A</creatorcontrib><creatorcontrib>Flatmark, Kjersti</creatorcontrib><title>Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Colorectal cancer (CRC) is one of the leading causes of cancer related deaths and the search for prognostic biomarkers that might improve treatment decisions is warranted. 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Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adenomatous polyposis coli</subject><subject>Analysis</subject><subject>Biology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cancer metastasis</subject><subject>Cluster Analysis</subject><subject>Colon</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Dihydrofolate reductase</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genomics</subject><subject>Hazard identification</subject><subject>Health aspects</subject><subject>High-Throughput Nucleotide Sequencing - 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genetics</topic><topic>Cancer</topic><topic>Cancer metastasis</topic><topic>Cluster Analysis</topic><topic>Colon</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Dihydrofolate reductase</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genomics</topic><topic>Hazard identification</topic><topic>Health aspects</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Informatics</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>miRNA</topic><topic>Non-coding RNA</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Proportional Hazards Models</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Rectum</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Statistical models</topic><topic>Studies</topic><topic>Surgery</topic><topic>Transcriptome</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schee, Kristina</creatorcontrib><creatorcontrib>Lorenz, Susanne</creatorcontrib><creatorcontrib>Worren, Merete Molton</creatorcontrib><creatorcontrib>Günther, Clara-Cecilie</creatorcontrib><creatorcontrib>Holden, Marit</creatorcontrib><creatorcontrib>Hovig, Eivind</creatorcontrib><creatorcontrib>Fodstad, Oystein</creatorcontrib><creatorcontrib>Meza-Zepeda, Leonardo A</creatorcontrib><creatorcontrib>Flatmark, Kjersti</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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MicroRNAs (miRNAs) are short non-coding RNA molecules involved in regulating gene expression and have been proposed as possible biomarkers in CRC. In order to characterize the miRNA transcriptome, a large cohort including 88 CRC tumors with long-term follow-up was deep sequenced. 523 mature miRNAs were expressed in our cohort, and they exhibited largely uniform expression patterns across tumor samples. Few associations were found between clinical parameters and miRNA expression, among them, low expression of miR-592 and high expression of miR-10b-5p and miR-615-3p were associated with tumors located in the right colon relative to the left colon and rectum. High expression of miR-615-3p was also associated with poorly differentiated tumors. No prognostic biomarker candidates for overall and metastasis-free survival were identified by applying the LASSO method in a Cox proportional hazards model or univariate Cox. Examination of the five most abundantly expressed miRNAs in the cohort (miR-10a-5p, miR-21-5p, miR-22-3p, miR-143-3p and miR-192-5p) revealed that their collective expression represented 54% of the detected miRNA sequences. Pathway analysis of the target genes regulated by the five most highly expressed miRNAs uncovered a significant number of genes involved in the CRC pathway, including APC, TGFβ and PI3K, thus suggesting that these miRNAs are relevant in CRC.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23824282</pmid><doi>10.1371/journal.pone.0066165</doi><tpages>e66165</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | PloS one, 2013-06, Vol.8 (6), p.e66165-e66165 |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Adenomatous polyposis coli Analysis Biology Biomarkers Biomarkers, Tumor - genetics Cancer Cancer metastasis Cluster Analysis Colon Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Dihydrofolate reductase Female Gene expression Gene sequencing Genes Genomics Hazard identification Health aspects High-Throughput Nucleotide Sequencing - methods Hospitals Humans Informatics Male Medical prognosis Medical research Medicine Metastases Metastasis MicroRNA MicroRNAs MicroRNAs - genetics miRNA Non-coding RNA Patients Prognosis Proportional Hazards Models Real-Time Polymerase Chain Reaction Rectum Ribonucleic acid RNA Statistical models Studies Surgery Transcriptome Tumors |
| title | Deep Sequencing the MicroRNA Transcriptome in Colorectal Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T19%3A52%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Deep%20Sequencing%20the%20MicroRNA%20Transcriptome%20in%20Colorectal%20Cancer&rft.jtitle=PloS%20one&rft.au=Schee,%20Kristina&rft.date=2013-06-18&rft.volume=8&rft.issue=6&rft.spage=e66165&rft.epage=e66165&rft.pages=e66165-e66165&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0066165&rft_dat=%3Cgale_plos_%3EA478225339%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1369310032&rft_id=info:pmid/23824282&rft_galeid=A478225339&rft_doaj_id=oai_doaj_org_article_9538d688bf6947ac923883ceb53ad52d&rfr_iscdi=true |