Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions
Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe co...
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| creator | Voorwald, Fabiana Azevedo Marchi, Fabio Albuquerque Villacis, Rolando Andre Rios Alves, Carlos Eduardo Fonseca Toniollo, Gilson Hélio Amorim, Renee Laufer Drigo, Sandra Aparecida Rogatto, Silvia Regina |
| description | Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity. |
| doi_str_mv | 10.1371/journal.pone.0133894 |
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This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0133894</identifier><identifier>PMID: 26222498</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Atherosclerosis ; Bacterial infections ; Biological markers ; Biomarkers ; Biomarkers - metabolism ; Cancer ; Care and treatment ; Cervix ; Cluster analysis ; CXCL10 protein ; Cyclooxygenase-2 ; Cytokines ; Disease ; Dog Diseases - drug therapy ; Dog Diseases - genetics ; Dogs ; Endometrial hyperplasia ; Endometrium ; Female ; Gene expression ; Gene Expression Profiling ; Genes ; Genetic aspects ; Hyperplasia ; Infections ; Inflammation ; Interleukin 1 ; Interleukin 6 ; Interleukin 8 ; Lesions ; Ligands ; Molecular Targeted Therapy ; Pathogenesis ; Physiological aspects ; Progesterone ; Proteins ; Pyometra - drug therapy ; Pyometra - genetics ; Pyometra - veterinary ; Ribonucleic acid ; Risk factors ; RNA ; Sepsis ; Studies ; Surgery ; Tumor necrosis factor ; Urology ; Uterus ; Veterinary medicine ; Veterinary services</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0133894-e0133894</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Voorwald 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>2015 Voorwald et al 2015 Voorwald et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-e4a29d76f1a575aa5c5c852f9b3a41c0c39a6dc58a40af274d0a42302e610fa3</citedby><cites>FETCH-LOGICAL-c692t-e4a29d76f1a575aa5c5c852f9b3a41c0c39a6dc58a40af274d0a42302e610fa3</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/PMC4519320/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519320/$$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/26222498$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Voorwald, Fabiana Azevedo</creatorcontrib><creatorcontrib>Marchi, Fabio Albuquerque</creatorcontrib><creatorcontrib>Villacis, Rolando Andre Rios</creatorcontrib><creatorcontrib>Alves, Carlos Eduardo Fonseca</creatorcontrib><creatorcontrib>Toniollo, Gilson Hélio</creatorcontrib><creatorcontrib>Amorim, Renee Laufer</creatorcontrib><creatorcontrib>Drigo, Sandra Aparecida</creatorcontrib><creatorcontrib>Rogatto, Silvia Regina</creatorcontrib><title>Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Cystic endometrial hyperplasia (CEH), mucometra, and pyometra are common uterine diseases in intact dogs, with pyometra being a life threatening disease. This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.</description><subject>Animals</subject><subject>Atherosclerosis</subject><subject>Bacterial infections</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Cancer</subject><subject>Care and treatment</subject><subject>Cervix</subject><subject>Cluster analysis</subject><subject>CXCL10 protein</subject><subject>Cyclooxygenase-2</subject><subject>Cytokines</subject><subject>Disease</subject><subject>Dog Diseases - drug therapy</subject><subject>Dog Diseases - genetics</subject><subject>Dogs</subject><subject>Endometrial hyperplasia</subject><subject>Endometrium</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Hyperplasia</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Interleukin 1</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Lesions</subject><subject>Ligands</subject><subject>Molecular Targeted Therapy</subject><subject>Pathogenesis</subject><subject>Physiological aspects</subject><subject>Progesterone</subject><subject>Proteins</subject><subject>Pyometra - drug therapy</subject><subject>Pyometra - genetics</subject><subject>Pyometra - veterinary</subject><subject>Ribonucleic acid</subject><subject>Risk factors</subject><subject>RNA</subject><subject>Sepsis</subject><subject>Studies</subject><subject>Surgery</subject><subject>Tumor necrosis factor</subject><subject>Urology</subject><subject>Uterus</subject><subject>Veterinary medicine</subject><subject>Veterinary services</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk19v0zAUxSMEYmPwDRBEQkLw0OL_SV6QRlWgUtGmUfFq3Tk3rUsaFzuZxrfHodnUoD2gPCRyfufY9_rcJHlJyZTyjH7Yus43UE_3rsEpoZznhXiUnNKCs4lihD8--j5JnoWwJUTyXKmnyQlTjDFR5KeJ--ZqNF0NPp3f7j2GYF2TXnpX2RrTK7xBqEN66VpsWgt1-sm6Hfif6EMKTZmuNuhhj11rTboCv8Y2pLZJZ9DYBtN5U7odtr4XLrF3Ds-TJ1V0xBfD-yxZfZ6vZl8ny4svi9n5cmJUwdoJCmBFmamKgswkgDTS5JJVxTUHQQ0xvABVGpmDIFCxTJQEBOOEoaKkAn6WvD7Y7msX9NCqoGlGCCVZnotILA5E6WCr997Gsn5rB1b_XXB-rcHHsmrUpTSMUMxlZlCoMna1NAwUk4qLkuUyen0cduuud1ia2CsP9ch0_KexG712N1rI_opINHg3GHj3q8PQ6p0NBusaGnTd4dwqF0rSiL75B324uoFaQyzANpWL-5reVJ8LKbnKCtafe_oAFZ8Sd9bEXPUhGAvejwSRafG2XUMXgl58v_p_9uLHmH17xG5i5tpNcHWMVYzMGBQH0HgXgsfqvsmU6H4s7rqh-7HQw1hE2avjC7oX3c0B_wNdYghn</recordid><startdate>20150729</startdate><enddate>20150729</enddate><creator>Voorwald, Fabiana Azevedo</creator><creator>Marchi, Fabio Albuquerque</creator><creator>Villacis, Rolando Andre Rios</creator><creator>Alves, Carlos Eduardo Fonseca</creator><creator>Toniollo, Gilson Hélio</creator><creator>Amorim, Renee Laufer</creator><creator>Drigo, Sandra Aparecida</creator><creator>Rogatto, Silvia Regina</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>AAYXX</scope><scope>CITATION</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>AEUYN</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>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150729</creationdate><title>Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions</title><author>Voorwald, Fabiana Azevedo ; Marchi, Fabio Albuquerque ; Villacis, Rolando Andre Rios ; Alves, Carlos Eduardo Fonseca ; Toniollo, Gilson Hélio ; Amorim, Renee Laufer ; Drigo, Sandra Aparecida ; Rogatto, Silvia Regina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-e4a29d76f1a575aa5c5c852f9b3a41c0c39a6dc58a40af274d0a42302e610fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Atherosclerosis</topic><topic>Bacterial infections</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers - 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This study aimed to determine the gene expression profile of these lesions and potential biomarkers for closed-cervix pyometra, the most severe condition. Total RNA was extracted from 69 fresh endometrium samples collected from 21 healthy female dogs during diestrus, 16 CEH, 15 mucometra and 17 pyometra (eight open and nine closed-cervixes). Global gene expression was detected using the Affymetrix Canine Gene 1.0 ST Array. Unsupervised analysis revealed two clusters, one mainly composed of diestrus and CEH samples and the other by 12/15 mucometra and all pyometra samples. When comparing pyometra with other groups, 189 differentially expressed genes were detected. SLPI, PTGS2/COX2, MMP1, S100A8, S100A9 and IL8 were among the top up-regulated genes detected in pyometra, further confirmed by external expression data. Notably, a particular molecular profile in pyometra from animals previously treated with exogenous progesterone compounds was observed in comparison with pyometra from untreated dogs as well as with other groups irrespective of exogenous hormone treatment status. In addition to S100A8 and S100A9 genes, overexpression of the inflammatory cytokines IL1B, TNF and IL6 as well as LTF were detected in the pyometra from treated animals. Interestingly, closed pyometra was more frequently detected in treated dogs (64% versus 33%), with IL1B, TNF, LBP and CXCL10 among the most relevant overexpressed genes. This molecular signature associated with potential biomarkers and therapeutic targets, such as CXCL10 and COX2, should guide future clinical studies. Based on the gene expression profile we suggested that pyometra from progesterone treated dogs is a distinct molecular entity.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26222498</pmid><doi>10.1371/journal.pone.0133894</doi><tpages>e0133894</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1700107884 |
| 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 | Animals Atherosclerosis Bacterial infections Biological markers Biomarkers Biomarkers - metabolism Cancer Care and treatment Cervix Cluster analysis CXCL10 protein Cyclooxygenase-2 Cytokines Disease Dog Diseases - drug therapy Dog Diseases - genetics Dogs Endometrial hyperplasia Endometrium Female Gene expression Gene Expression Profiling Genes Genetic aspects Hyperplasia Infections Inflammation Interleukin 1 Interleukin 6 Interleukin 8 Lesions Ligands Molecular Targeted Therapy Pathogenesis Physiological aspects Progesterone Proteins Pyometra - drug therapy Pyometra - genetics Pyometra - veterinary Ribonucleic acid Risk factors RNA Sepsis Studies Surgery Tumor necrosis factor Urology Uterus Veterinary medicine Veterinary services |
| title | Molecular Expression Profile Reveals Potential Biomarkers and Therapeutic Targets in Canine Endometrial Lesions |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T21%3A45%3A25IST&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=Molecular%20Expression%20Profile%20Reveals%20Potential%20Biomarkers%20and%20Therapeutic%20Targets%20in%20Canine%20Endometrial%20Lesions&rft.jtitle=PloS%20one&rft.au=Voorwald,%20Fabiana%20Azevedo&rft.date=2015-07-29&rft.volume=10&rft.issue=7&rft.spage=e0133894&rft.epage=e0133894&rft.pages=e0133894-e0133894&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0133894&rft_dat=%3Cgale_plos_%3EA455367925%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=1700107884&rft_id=info:pmid/26222498&rft_galeid=A455367925&rft_doaj_id=oai_doaj_org_article_d5c201e857ce46d193dc2a625634d285&rfr_iscdi=true |