A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema
(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF...
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| Veröffentlicht in: | Journal of clinical medicine 2020-09, Vol.9 (9), p.2920 |
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| creator | Chan, Hwei Wuen Yang, Binxia Wong, Wendy Blakeley, Paul Seah, Ivan Tan, Queenie Shu Woon Wang, Haofei Bhargava, Mayuri Lin, Hazel Anne Chai, Charmaine Hc Mangunkusumo, Erlangga Ariadarma Thet, Naing Yuen, Yew Sen Sethi, Raman Wang, Si Hunziker, Walter Lingam, Gopal Su, Xinyi |
| description | (1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (
= 315), followed by serum (
= 309), then aqueous humor (
= 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers. |
| doi_str_mv | 10.3390/jcm9092920 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2442841007</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2641059175</sourcerecordid><originalsourceid>FETCH-LOGICAL-c406t-6b44f8edd2274aca83b7db41547b06f59fd8fdd348ab5a417a72c6528be7426d3</originalsourceid><addsrcrecordid>eNpdkV9LHDEUxUOpVFFf_AAl4EsRRjNJZpJ5EZbtrha0Lbr2NWSSO22Wmck2yQh-e7P4p9r7ksu9Pw7n5iB0VJJTxhpytjZDQxraUPIB7VEiREGYZB_f9LvoMMY1ySUlp6X4hHZZ5oWQZA_dz_BP1_uEb9NkH7Af8bUzwd98z_PgO9cDdiNegQ542U_O4uTzAqwzCd9A3PgxwnY2G5Mrfi0ulngVQKcBxhRx5wP-6nQLyRl8rc3UZ5mFhUEfoJ1O9xEOn999dLdcrOaXxdWPi2_z2VVhOKlTUbecdxKspVRwbbRkrbAtLysuWlJ3VdNZ2VnLuNRtpXkptKCmrqhsQXBaW7aPzp90N1M7gDXZVtC92gQ36PCgvHbq_WZ0f9Rvf69EVXNWV1ngy7NA8H8niEkNLhroez2Cn6KinFPJS0JERo__Q9d-CmM-T9E6I1VTiq3gyROVfznGAN2rmZKobaLqX6IZ_vzW_iv6kh97BHlZm1k</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2641059175</pqid></control><display><type>article</type><title>A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema</title><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Chan, Hwei Wuen ; Yang, Binxia ; Wong, Wendy ; Blakeley, Paul ; Seah, Ivan ; Tan, Queenie Shu Woon ; Wang, Haofei ; Bhargava, Mayuri ; Lin, Hazel Anne ; Chai, Charmaine Hc ; Mangunkusumo, Erlangga Ariadarma ; Thet, Naing ; Yuen, Yew Sen ; Sethi, Raman ; Wang, Si ; Hunziker, Walter ; Lingam, Gopal ; Su, Xinyi</creator><creatorcontrib>Chan, Hwei Wuen ; Yang, Binxia ; Wong, Wendy ; Blakeley, Paul ; Seah, Ivan ; Tan, Queenie Shu Woon ; Wang, Haofei ; Bhargava, Mayuri ; Lin, Hazel Anne ; Chai, Charmaine Hc ; Mangunkusumo, Erlangga Ariadarma ; Thet, Naing ; Yuen, Yew Sen ; Sethi, Raman ; Wang, Si ; Hunziker, Walter ; Lingam, Gopal ; Su, Xinyi</creatorcontrib><description>(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (
= 315), followed by serum (
= 309), then aqueous humor (
= 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.</description><identifier>ISSN: 2077-0383</identifier><identifier>EISSN: 2077-0383</identifier><identifier>DOI: 10.3390/jcm9092920</identifier><identifier>PMID: 32927780</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biomarkers ; Clinical medicine ; Diabetes ; Diabetic retinopathy ; Edema ; Gene expression ; Homeostasis ; MicroRNAs ; Monoclonal antibodies ; Patients ; Vascular endothelial growth factor</subject><ispartof>Journal of clinical medicine, 2020-09, Vol.9 (9), p.2920</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-6b44f8edd2274aca83b7db41547b06f59fd8fdd348ab5a417a72c6528be7426d3</citedby><cites>FETCH-LOGICAL-c406t-6b44f8edd2274aca83b7db41547b06f59fd8fdd348ab5a417a72c6528be7426d3</cites><orcidid>0000-0002-1480-6713 ; 0000-0001-8079-8398 ; 0000-0001-7843-1917 ; 0000-0001-8914-442X ; 0000-0002-4514-250X</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/PMC7564365/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564365/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32927780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Hwei Wuen</creatorcontrib><creatorcontrib>Yang, Binxia</creatorcontrib><creatorcontrib>Wong, Wendy</creatorcontrib><creatorcontrib>Blakeley, Paul</creatorcontrib><creatorcontrib>Seah, Ivan</creatorcontrib><creatorcontrib>Tan, Queenie Shu Woon</creatorcontrib><creatorcontrib>Wang, Haofei</creatorcontrib><creatorcontrib>Bhargava, Mayuri</creatorcontrib><creatorcontrib>Lin, Hazel Anne</creatorcontrib><creatorcontrib>Chai, Charmaine Hc</creatorcontrib><creatorcontrib>Mangunkusumo, Erlangga Ariadarma</creatorcontrib><creatorcontrib>Thet, Naing</creatorcontrib><creatorcontrib>Yuen, Yew Sen</creatorcontrib><creatorcontrib>Sethi, Raman</creatorcontrib><creatorcontrib>Wang, Si</creatorcontrib><creatorcontrib>Hunziker, Walter</creatorcontrib><creatorcontrib>Lingam, Gopal</creatorcontrib><creatorcontrib>Su, Xinyi</creatorcontrib><title>A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema</title><title>Journal of clinical medicine</title><addtitle>J Clin Med</addtitle><description>(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (
= 315), followed by serum (
= 309), then aqueous humor (
= 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.</description><subject>Biomarkers</subject><subject>Clinical medicine</subject><subject>Diabetes</subject><subject>Diabetic retinopathy</subject><subject>Edema</subject><subject>Gene expression</subject><subject>Homeostasis</subject><subject>MicroRNAs</subject><subject>Monoclonal antibodies</subject><subject>Patients</subject><subject>Vascular endothelial growth factor</subject><issn>2077-0383</issn><issn>2077-0383</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNpdkV9LHDEUxUOpVFFf_AAl4EsRRjNJZpJ5EZbtrha0Lbr2NWSSO22Wmck2yQh-e7P4p9r7ksu9Pw7n5iB0VJJTxhpytjZDQxraUPIB7VEiREGYZB_f9LvoMMY1ySUlp6X4hHZZ5oWQZA_dz_BP1_uEb9NkH7Af8bUzwd98z_PgO9cDdiNegQ542U_O4uTzAqwzCd9A3PgxwnY2G5Mrfi0ulngVQKcBxhRx5wP-6nQLyRl8rc3UZ5mFhUEfoJ1O9xEOn999dLdcrOaXxdWPi2_z2VVhOKlTUbecdxKspVRwbbRkrbAtLysuWlJ3VdNZ2VnLuNRtpXkptKCmrqhsQXBaW7aPzp90N1M7gDXZVtC92gQ36PCgvHbq_WZ0f9Rvf69EVXNWV1ngy7NA8H8niEkNLhroez2Cn6KinFPJS0JERo__Q9d-CmM-T9E6I1VTiq3gyROVfznGAN2rmZKobaLqX6IZ_vzW_iv6kh97BHlZm1k</recordid><startdate>20200910</startdate><enddate>20200910</enddate><creator>Chan, Hwei Wuen</creator><creator>Yang, Binxia</creator><creator>Wong, Wendy</creator><creator>Blakeley, Paul</creator><creator>Seah, Ivan</creator><creator>Tan, Queenie Shu Woon</creator><creator>Wang, Haofei</creator><creator>Bhargava, Mayuri</creator><creator>Lin, Hazel Anne</creator><creator>Chai, Charmaine Hc</creator><creator>Mangunkusumo, Erlangga Ariadarma</creator><creator>Thet, Naing</creator><creator>Yuen, Yew Sen</creator><creator>Sethi, Raman</creator><creator>Wang, Si</creator><creator>Hunziker, Walter</creator><creator>Lingam, Gopal</creator><creator>Su, Xinyi</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1480-6713</orcidid><orcidid>https://orcid.org/0000-0001-8079-8398</orcidid><orcidid>https://orcid.org/0000-0001-7843-1917</orcidid><orcidid>https://orcid.org/0000-0001-8914-442X</orcidid><orcidid>https://orcid.org/0000-0002-4514-250X</orcidid></search><sort><creationdate>20200910</creationdate><title>A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema</title><author>Chan, Hwei Wuen ; Yang, Binxia ; Wong, Wendy ; Blakeley, Paul ; Seah, Ivan ; Tan, Queenie Shu Woon ; Wang, Haofei ; Bhargava, Mayuri ; Lin, Hazel Anne ; Chai, Charmaine Hc ; Mangunkusumo, Erlangga Ariadarma ; Thet, Naing ; Yuen, Yew Sen ; Sethi, Raman ; Wang, Si ; Hunziker, Walter ; Lingam, Gopal ; Su, Xinyi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-6b44f8edd2274aca83b7db41547b06f59fd8fdd348ab5a417a72c6528be7426d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biomarkers</topic><topic>Clinical medicine</topic><topic>Diabetes</topic><topic>Diabetic retinopathy</topic><topic>Edema</topic><topic>Gene expression</topic><topic>Homeostasis</topic><topic>MicroRNAs</topic><topic>Monoclonal antibodies</topic><topic>Patients</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chan, Hwei Wuen</creatorcontrib><creatorcontrib>Yang, Binxia</creatorcontrib><creatorcontrib>Wong, Wendy</creatorcontrib><creatorcontrib>Blakeley, Paul</creatorcontrib><creatorcontrib>Seah, Ivan</creatorcontrib><creatorcontrib>Tan, Queenie Shu Woon</creatorcontrib><creatorcontrib>Wang, Haofei</creatorcontrib><creatorcontrib>Bhargava, Mayuri</creatorcontrib><creatorcontrib>Lin, Hazel Anne</creatorcontrib><creatorcontrib>Chai, Charmaine Hc</creatorcontrib><creatorcontrib>Mangunkusumo, Erlangga Ariadarma</creatorcontrib><creatorcontrib>Thet, Naing</creatorcontrib><creatorcontrib>Yuen, Yew Sen</creatorcontrib><creatorcontrib>Sethi, Raman</creatorcontrib><creatorcontrib>Wang, Si</creatorcontrib><creatorcontrib>Hunziker, Walter</creatorcontrib><creatorcontrib>Lingam, Gopal</creatorcontrib><creatorcontrib>Su, Xinyi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chan, Hwei Wuen</au><au>Yang, Binxia</au><au>Wong, Wendy</au><au>Blakeley, Paul</au><au>Seah, Ivan</au><au>Tan, Queenie Shu Woon</au><au>Wang, Haofei</au><au>Bhargava, Mayuri</au><au>Lin, Hazel Anne</au><au>Chai, Charmaine Hc</au><au>Mangunkusumo, Erlangga Ariadarma</au><au>Thet, Naing</au><au>Yuen, Yew Sen</au><au>Sethi, Raman</au><au>Wang, Si</au><au>Hunziker, Walter</au><au>Lingam, Gopal</au><au>Su, Xinyi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema</atitle><jtitle>Journal of clinical medicine</jtitle><addtitle>J Clin Med</addtitle><date>2020-09-10</date><risdate>2020</risdate><volume>9</volume><issue>9</issue><spage>2920</spage><pages>2920-</pages><issn>2077-0383</issn><eissn>2077-0383</eissn><abstract>(1) Background: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) is an established treatment for center-involving diabetic macular edema (ci-DME). However, the clinical response is heterogeneous. This study investigated miRNAs as a biomarker to predict treatment response to anti-VEGF in DME. (2) Methods: Tear fluid, aqueous, and blood were collected from patients with treatment-naïve DME for miRNA expression profiling with quantitative polymerase chain reaction. Differentially expressed miRNAs between good and poor responders were identified from tear fluid. Bioinformatics analysis with the miEAA tool, miRTarBase Annotations, Gene Ontology categories, KEGG, and miRWalk pathways identified interactions between enriched miRNAs and biological pathways. (3) Results: Of 24 participants, 28 eyes received bevacizumab (15 eyes) or aflibercept (13 eyes). Tear fluid had the most detectable miRNA species (
= 315), followed by serum (
= 309), then aqueous humor (
= 134). MiRNAs that correlated with change in macular thickness were miR-214-3p, miR-320d, and hsa-miR-874-3p in good responders; and miR-98-5p, miR-196b-5p, and miR-454-3p in poor responders. VEGF-related pathways and the angiogenin-PRI complex were enriched in good responders, while transforming growth factor-β and insulin-like growth factor pathways were enriched in poor responders. (4) Conclusions: We reported a panel of novel miRNAs that provide insight into biological pathways in DME. Validation in larger independent cohorts is needed to determine the predictive performance of these miRNA candidate biomarkers.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32927780</pmid><doi>10.3390/jcm9092920</doi><orcidid>https://orcid.org/0000-0002-1480-6713</orcidid><orcidid>https://orcid.org/0000-0001-8079-8398</orcidid><orcidid>https://orcid.org/0000-0001-7843-1917</orcidid><orcidid>https://orcid.org/0000-0001-8914-442X</orcidid><orcidid>https://orcid.org/0000-0002-4514-250X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Biomarkers Clinical medicine Diabetes Diabetic retinopathy Edema Gene expression Homeostasis MicroRNAs Monoclonal antibodies Patients Vascular endothelial growth factor |
| title | A Pilot Study on MicroRNA Profile in Tear Fluid to Predict Response to Anti-VEGF Treatments for Diabetic Macular Edema |
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