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Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD t...
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Published in: | Lipids in health and disease 2021-11, Vol.20 (1), p.155-155, Article 155 |
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description | Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention.
In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed.
A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported.
The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention. |
doi_str_mv | 10.1186/s12944-021-01578-7 |
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In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed.
A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported.
The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.</description><identifier>ISSN: 1476-511X</identifier><identifier>EISSN: 1476-511X</identifier><identifier>DOI: 10.1186/s12944-021-01578-7</identifier><identifier>PMID: 34742290</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>alpha-Synuclein - blood ; Alzheimer's disease ; Autism ; Autism Spectrum Disorder - blood ; Autism Spectrum Disorder - diagnosis ; Biological markers ; Biomarkers ; Biomarkers - blood ; Case-Control Studies ; Child, Preschool ; Children ; Consent ; Cyclooxygenase 2 - blood ; Cyclooxygenase-2 ; Cyclooxygenases ; Development and progression ; Diagnosis ; Enzymes ; Ethics ; Etiology ; Health aspects ; Humans ; Identification and classification ; Inflammation ; Lipid metabolism ; Lipids ; Male ; Nerve proteins ; Neurodevelopmental disorders ; Neuroinflammation ; Neuroinflammatory Diseases - blood ; Neurological disorders ; Neurotoxicity ; Oxygenase ; Pervasive developmental disorders ; Physiological aspects ; Plasma ; Prostaglandin endoperoxide synthase ; Prostaglandin-EP2 receptors ; Prostaglandins ; Proteins ; Receptors, Prostaglandin E, EP2 Subtype - blood ; Regression analysis ; ROC Curve ; Signal transduction ; Statistical analysis ; Synuclein ; α-Synuclein</subject><ispartof>Lipids in health and disease, 2021-11, Vol.20 (1), p.155-155, Article 155</ispartof><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2021 BioMed Central Ltd.</rights><rights>2021. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c563t-d4784b052f21328ae19f25be766a27abe674730aca030a20e2670df7d18a61fe3</citedby><cites>FETCH-LOGICAL-c563t-d4784b052f21328ae19f25be766a27abe674730aca030a20e2670df7d18a61fe3</cites><orcidid>0000-0002-1404-5248</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571879/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2599178358?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25732,27903,27904,36991,36992,44569,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34742290$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Ansary, Afaf</creatorcontrib><creatorcontrib>Alhakbany, Manan</creatorcontrib><creatorcontrib>Aldbass, Abeer</creatorcontrib><creatorcontrib>Qasem, Hanan</creatorcontrib><creatorcontrib>Al-Mazidi, Sarah</creatorcontrib><creatorcontrib>Bhat, Ramesa Shafi</creatorcontrib><creatorcontrib>Al-Ayadhi, Laila</creatorcontrib><title>Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values</title><title>Lipids in health and disease</title><addtitle>Lipids Health Dis</addtitle><description>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention.
In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed.
A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported.
The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.</description><subject>alpha-Synuclein - blood</subject><subject>Alzheimer's disease</subject><subject>Autism</subject><subject>Autism Spectrum Disorder - blood</subject><subject>Autism Spectrum Disorder - diagnosis</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Case-Control Studies</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Consent</subject><subject>Cyclooxygenase 2 - blood</subject><subject>Cyclooxygenase-2</subject><subject>Cyclooxygenases</subject><subject>Development and progression</subject><subject>Diagnosis</subject><subject>Enzymes</subject><subject>Ethics</subject><subject>Etiology</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Inflammation</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Male</subject><subject>Nerve proteins</subject><subject>Neurodevelopmental disorders</subject><subject>Neuroinflammation</subject><subject>Neuroinflammatory Diseases - blood</subject><subject>Neurological disorders</subject><subject>Neurotoxicity</subject><subject>Oxygenase</subject><subject>Pervasive developmental disorders</subject><subject>Physiological aspects</subject><subject>Plasma</subject><subject>Prostaglandin endoperoxide synthase</subject><subject>Prostaglandin-EP2 receptors</subject><subject>Prostaglandins</subject><subject>Proteins</subject><subject>Receptors, Prostaglandin E, EP2 Subtype - blood</subject><subject>Regression analysis</subject><subject>ROC Curve</subject><subject>Signal transduction</subject><subject>Statistical analysis</subject><subject>Synuclein</subject><subject>α-Synuclein</subject><issn>1476-511X</issn><issn>1476-511X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptUk1v1DAQjRCIlsIf4IAsceFAiu0kdsIBabUqUKlSEVCJm-XYk6xLYi92smJ_HX-N2W4pXYQsxdbMey_z8bLsOaOnjNXiTWK8KcuccpZTVsk6lw-yY1ZKkVeMfXt4732UPUnpmlJOpRCPs6OilCXnDT3Ofi2G9UrnX7Z-NgM4_5qYrRlC-LntwesEOSfaW7KOIU26H_DtfMrPPnESwcB6CjERnYiHOQbnu0GPo8bglrQujDp-B8yHjuh5cmkkaQ1mivNIrEshWky-JVcJdggTxtZ5sOTz5ZKYOW4gkSkQ500ErINMK3ARebr3WIozZKOHGdLT7FGnhwTPbu-T7Or92dflx_zi8sP5cnGRm0oUU25LWZctrXjHWcFrDazpeNUCjkNzqVsQspQF1UZT_HIKXEhqO2lZrQXroDjJzve6NuhrtY4Om9uqoJ26CYTYKx2xrAEUazvGuWVlUZiS2aqhhWiEkVK0tWiZQa13e6313I5gDfgp6uFA9DDj3Ur1YaPqSrJaNijw6lYghh84hEmNLhkYcD0Q5qR41eDWa8kpQl_-A70Oc_Q4qh2qYbIuqvovqtfYAO4x4H_NTlQtRM2E4AUvEXX6HxQeC6MzwUPnMH5A4HuCQfukCN1dj4yqnYXV3sIKLaxuLKwkkl7cn84d5Y9ni9_Eru9K</recordid><startdate>20211106</startdate><enddate>20211106</enddate><creator>El-Ansary, Afaf</creator><creator>Alhakbany, Manan</creator><creator>Aldbass, Abeer</creator><creator>Qasem, Hanan</creator><creator>Al-Mazidi, Sarah</creator><creator>Bhat, Ramesa Shafi</creator><creator>Al-Ayadhi, Laila</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1404-5248</orcidid></search><sort><creationdate>20211106</creationdate><title>Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values</title><author>El-Ansary, Afaf ; Alhakbany, Manan ; Aldbass, Abeer ; Qasem, Hanan ; Al-Mazidi, Sarah ; Bhat, Ramesa Shafi ; Al-Ayadhi, Laila</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c563t-d4784b052f21328ae19f25be766a27abe674730aca030a20e2670df7d18a61fe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>alpha-Synuclein - blood</topic><topic>Alzheimer's disease</topic><topic>Autism</topic><topic>Autism Spectrum Disorder - blood</topic><topic>Autism Spectrum Disorder - diagnosis</topic><topic>Biological markers</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Case-Control Studies</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Consent</topic><topic>Cyclooxygenase 2 - blood</topic><topic>Cyclooxygenase-2</topic><topic>Cyclooxygenases</topic><topic>Development and progression</topic><topic>Diagnosis</topic><topic>Enzymes</topic><topic>Ethics</topic><topic>Etiology</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Inflammation</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Male</topic><topic>Nerve proteins</topic><topic>Neurodevelopmental disorders</topic><topic>Neuroinflammation</topic><topic>Neuroinflammatory Diseases - blood</topic><topic>Neurological disorders</topic><topic>Neurotoxicity</topic><topic>Oxygenase</topic><topic>Pervasive developmental disorders</topic><topic>Physiological aspects</topic><topic>Plasma</topic><topic>Prostaglandin endoperoxide synthase</topic><topic>Prostaglandin-EP2 receptors</topic><topic>Prostaglandins</topic><topic>Proteins</topic><topic>Receptors, Prostaglandin E, EP2 Subtype - blood</topic><topic>Regression analysis</topic><topic>ROC Curve</topic><topic>Signal transduction</topic><topic>Statistical analysis</topic><topic>Synuclein</topic><topic>α-Synuclein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>El-Ansary, Afaf</creatorcontrib><creatorcontrib>Alhakbany, Manan</creatorcontrib><creatorcontrib>Aldbass, Abeer</creatorcontrib><creatorcontrib>Qasem, Hanan</creatorcontrib><creatorcontrib>Al-Mazidi, Sarah</creatorcontrib><creatorcontrib>Bhat, Ramesa Shafi</creatorcontrib><creatorcontrib>Al-Ayadhi, Laila</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Lipids in health and disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Ansary, Afaf</au><au>Alhakbany, Manan</au><au>Aldbass, Abeer</au><au>Qasem, Hanan</au><au>Al-Mazidi, Sarah</au><au>Bhat, Ramesa Shafi</au><au>Al-Ayadhi, Laila</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values</atitle><jtitle>Lipids in health and disease</jtitle><addtitle>Lipids Health Dis</addtitle><date>2021-11-06</date><risdate>2021</risdate><volume>20</volume><issue>1</issue><spage>155</spage><epage>155</epage><pages>155-155</pages><artnum>155</artnum><issn>1476-511X</issn><eissn>1476-511X</eissn><abstract>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention.
In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed.
A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported.
The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>34742290</pmid><doi>10.1186/s12944-021-01578-7</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1404-5248</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | alpha-Synuclein - blood Alzheimer's disease Autism Autism Spectrum Disorder - blood Autism Spectrum Disorder - diagnosis Biological markers Biomarkers Biomarkers - blood Case-Control Studies Child, Preschool Children Consent Cyclooxygenase 2 - blood Cyclooxygenase-2 Cyclooxygenases Development and progression Diagnosis Enzymes Ethics Etiology Health aspects Humans Identification and classification Inflammation Lipid metabolism Lipids Male Nerve proteins Neurodevelopmental disorders Neuroinflammation Neuroinflammatory Diseases - blood Neurological disorders Neurotoxicity Oxygenase Pervasive developmental disorders Physiological aspects Plasma Prostaglandin endoperoxide synthase Prostaglandin-EP2 receptors Prostaglandins Proteins Receptors, Prostaglandin E, EP2 Subtype - blood Regression analysis ROC Curve Signal transduction Statistical analysis Synuclein α-Synuclein |
title | Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values |
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