Profiling of Small Nucleolar RNAs by Next Generation Sequencing: Potential New Players for Breast Cancer Prognosis
One of the most abundant, yet least explored, classes of RNA is the small nucleolar RNAs (snoRNAs), which are well known for their involvement in post-transcriptional modifications of other RNAs. Although snoRNAs were only considered to perform housekeeping functions for a long time, recent studies...
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| description | One of the most abundant, yet least explored, classes of RNA is the small nucleolar RNAs (snoRNAs), which are well known for their involvement in post-transcriptional modifications of other RNAs. Although snoRNAs were only considered to perform housekeeping functions for a long time, recent studies have highlighted their importance as regulators of gene expression and as diagnostic/prognostic markers. However, the prognostic potential of these RNAs has not been interrogated for breast cancer (BC). The objective of the current study was to identify snoRNAs as prognostic markers for BC. Small RNA sequencing (Illumina Genome Analyzer IIx) was performed for 104 BC cases and 11 normal breast tissues. Partek Genomics Suite was used for analyzing the sequencing files. Two independent and proven approaches were used to identify prognostic markers: case-control (CC) and case-only (CO). For both approaches, snoRNAs significant in the permutation test, following univariate Cox proportional hazards regression model were used for constructing risk scores. Risk scores were subsequently adjusted for potential confounders in a multivariate Cox model. For both approaches, thirteen snoRNAs were associated with overall survival and/or recurrence free survival. Patients belonging to the high-risk group were associated with poor outcomes, and the risk score was significant after adjusting for confounders. Validation of representative snoRNAs (SNORD46 and SNORD89) using qRT-PCR confirmed the observations from sequencing experiments. We also observed 64 snoRNAs harboring piwi-interacting RNAs and/or microRNAs that were predicted to target genes (mRNAs) involved in tumorigenesis. Our results demonstrate the potential of snoRNAs to serve (i) as novel prognostic markers for BC and (ii) as indirect regulators of gene expression. |
| doi_str_mv | 10.1371/journal.pone.0162622 |
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Although snoRNAs were only considered to perform housekeeping functions for a long time, recent studies have highlighted their importance as regulators of gene expression and as diagnostic/prognostic markers. However, the prognostic potential of these RNAs has not been interrogated for breast cancer (BC). The objective of the current study was to identify snoRNAs as prognostic markers for BC. Small RNA sequencing (Illumina Genome Analyzer IIx) was performed for 104 BC cases and 11 normal breast tissues. Partek Genomics Suite was used for analyzing the sequencing files. Two independent and proven approaches were used to identify prognostic markers: case-control (CC) and case-only (CO). For both approaches, snoRNAs significant in the permutation test, following univariate Cox proportional hazards regression model were used for constructing risk scores. Risk scores were subsequently adjusted for potential confounders in a multivariate Cox model. For both approaches, thirteen snoRNAs were associated with overall survival and/or recurrence free survival. Patients belonging to the high-risk group were associated with poor outcomes, and the risk score was significant after adjusting for confounders. Validation of representative snoRNAs (SNORD46 and SNORD89) using qRT-PCR confirmed the observations from sequencing experiments. We also observed 64 snoRNAs harboring piwi-interacting RNAs and/or microRNAs that were predicted to target genes (mRNAs) involved in tumorigenesis. Our results demonstrate the potential of snoRNAs to serve (i) as novel prognostic markers for BC and (ii) as indirect regulators of gene expression.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0162622</identifier><identifier>PMID: 27631501</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Biology and life sciences ; Biomarkers ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer ; Cancer research ; Colorectal cancer ; Diagnostic systems ; Ethics ; Female ; Gene expression ; Gene sequencing ; Genes ; Genomes ; Genomics ; Hazards ; Health services ; High-Throughput Nucleotide Sequencing ; Humans ; Laboratories ; Markers ; Medical prognosis ; Medical research ; MicroRNAs ; miRNA ; Nucleoli ; Oncology ; Pathology ; Permutations ; Post-transcription ; Prognosis ; Proportional Hazards Models ; Proteins ; Quality of life ; Regression analysis ; Regression models ; Regulators ; Research and analysis methods ; Ribonucleic acid ; Risk ; Risk groups ; RNA ; RNA sequencing ; RNA, Small Nucleolar - genetics ; snoRNA ; Survival ; Tissues ; Transcription (Genetics) ; Tumorigenesis</subject><ispartof>PloS one, 2016-09, Vol.11 (9), p.e0162622-e0162622</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Krishnan 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>2016 Krishnan et al 2016 Krishnan et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-b1846d7209984a7fbd25547ff02930584699e5bb51b8d2ee894cc080ec889413</citedby><cites>FETCH-LOGICAL-c725t-b1846d7209984a7fbd25547ff02930584699e5bb51b8d2ee894cc080ec889413</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/PMC5025248/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025248/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27631501$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krishnan, Preethi</creatorcontrib><creatorcontrib>Ghosh, Sunita</creatorcontrib><creatorcontrib>Wang, Bo</creatorcontrib><creatorcontrib>Heyns, Mieke</creatorcontrib><creatorcontrib>Graham, Kathryn</creatorcontrib><creatorcontrib>Mackey, John R</creatorcontrib><creatorcontrib>Kovalchuk, Olga</creatorcontrib><creatorcontrib>Damaraju, Sambasivarao</creatorcontrib><title>Profiling of Small Nucleolar RNAs by Next Generation Sequencing: Potential New Players for Breast Cancer Prognosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>One of the most abundant, yet least explored, classes of RNA is the small nucleolar RNAs (snoRNAs), which are well known for their involvement in post-transcriptional modifications of other RNAs. 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Our results demonstrate the potential of snoRNAs to serve (i) as novel prognostic markers for BC and (ii) as indirect regulators of gene expression.</description><subject>Analysis</subject><subject>Biology and life sciences</subject><subject>Biomarkers</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Cancer research</subject><subject>Colorectal cancer</subject><subject>Diagnostic systems</subject><subject>Ethics</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Hazards</subject><subject>Health services</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Markers</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Nucleoli</subject><subject>Oncology</subject><subject>Pathology</subject><subject>Permutations</subject><subject>Post-transcription</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Proteins</subject><subject>Quality of life</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Regulators</subject><subject>Research and analysis methods</subject><subject>Ribonucleic acid</subject><subject>Risk</subject><subject>Risk groups</subject><subject>RNA</subject><subject>RNA sequencing</subject><subject>RNA, Small Nucleolar - 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Although snoRNAs were only considered to perform housekeeping functions for a long time, recent studies have highlighted their importance as regulators of gene expression and as diagnostic/prognostic markers. However, the prognostic potential of these RNAs has not been interrogated for breast cancer (BC). The objective of the current study was to identify snoRNAs as prognostic markers for BC. Small RNA sequencing (Illumina Genome Analyzer IIx) was performed for 104 BC cases and 11 normal breast tissues. Partek Genomics Suite was used for analyzing the sequencing files. Two independent and proven approaches were used to identify prognostic markers: case-control (CC) and case-only (CO). For both approaches, snoRNAs significant in the permutation test, following univariate Cox proportional hazards regression model were used for constructing risk scores. Risk scores were subsequently adjusted for potential confounders in a multivariate Cox model. For both approaches, thirteen snoRNAs were associated with overall survival and/or recurrence free survival. Patients belonging to the high-risk group were associated with poor outcomes, and the risk score was significant after adjusting for confounders. Validation of representative snoRNAs (SNORD46 and SNORD89) using qRT-PCR confirmed the observations from sequencing experiments. We also observed 64 snoRNAs harboring piwi-interacting RNAs and/or microRNAs that were predicted to target genes (mRNAs) involved in tumorigenesis. Our results demonstrate the potential of snoRNAs to serve (i) as novel prognostic markers for BC and (ii) as indirect regulators of gene expression.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27631501</pmid><doi>10.1371/journal.pone.0162622</doi><tpages>e0162622</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2016-09, Vol.11 (9), p.e0162622-e0162622 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1819907167 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; PubMed Central; Directory of Open Access Journals; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Analysis Biology and life sciences Biomarkers Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Cancer research Colorectal cancer Diagnostic systems Ethics Female Gene expression Gene sequencing Genes Genomes Genomics Hazards Health services High-Throughput Nucleotide Sequencing Humans Laboratories Markers Medical prognosis Medical research MicroRNAs miRNA Nucleoli Oncology Pathology Permutations Post-transcription Prognosis Proportional Hazards Models Proteins Quality of life Regression analysis Regression models Regulators Research and analysis methods Ribonucleic acid Risk Risk groups RNA RNA sequencing RNA, Small Nucleolar - genetics snoRNA Survival Tissues Transcription (Genetics) Tumorigenesis |
| title | Profiling of Small Nucleolar RNAs by Next Generation Sequencing: Potential New Players for Breast Cancer Prognosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T15%3A44%3A41IST&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=Profiling%20of%20Small%20Nucleolar%20RNAs%20by%20Next%20Generation%20Sequencing:%20Potential%20New%20Players%20for%20Breast%20Cancer%20Prognosis&rft.jtitle=PloS%20one&rft.au=Krishnan,%20Preethi&rft.date=2016-09-15&rft.volume=11&rft.issue=9&rft.spage=e0162622&rft.epage=e0162622&rft.pages=e0162622-e0162622&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0162622&rft_dat=%3Cgale_plos_%3EA470941225%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=1819907167&rft_id=info:pmid/27631501&rft_galeid=A470941225&rft_doaj_id=oai_doaj_org_article_be5d7211448748508171af75423da98d&rfr_iscdi=true |