miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly
Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication presc...
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| Veröffentlicht in: | International journal of molecular sciences 2023-02, Vol.24 (3), p.2875 |
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| creator | Henriques, Daniel G Miranda, Renan Lyra Dezonne, Rômulo Sperduto Wildemberg, Luiz Eduardo Camacho, Aline Helen da Silva Chimelli, Leila Kasuki, Leandro Lamback, Elisa B Guterres, Alexandro Gadelha, Monica R |
| description | Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions. |
| doi_str_mv | 10.3390/ijms24032875 |
| format | Article |
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When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms24032875</identifier><identifier>PMID: 36769196</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acromegaly ; Acromegaly - genetics ; Adenoma ; Biomarkers ; Brain cancer ; Disease control ; Gene regulation ; Health services ; Humans ; Insulin-like growth factors ; Ligands ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - therapeutic use ; miRNA ; Pituitary gland ; Post-transcription ; Prediction models ; Receptors, Somatostatin - genetics ; Somatostatin ; Statistical significance ; Surgery ; Tumorigenesis ; Tumors</subject><ispartof>International journal of molecular sciences, 2023-02, Vol.24 (3), p.2875</ispartof><rights>2023 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 (https://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>2023 by the authors. 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-e65c11335f544e22387bace18bea7a42f47ffd6c8f45e0e883c4a98c44ec743e3</citedby><cites>FETCH-LOGICAL-c412t-e65c11335f544e22387bace18bea7a42f47ffd6c8f45e0e883c4a98c44ec743e3</cites><orcidid>0000-0002-5838-0881 ; 0000-0003-1339-3192 ; 0000-0001-9514-0986 ; 0000-0001-8323-1477</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/PMC9918086/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9918086/$$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/36769196$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Henriques, Daniel G</creatorcontrib><creatorcontrib>Miranda, Renan Lyra</creatorcontrib><creatorcontrib>Dezonne, Rômulo Sperduto</creatorcontrib><creatorcontrib>Wildemberg, Luiz Eduardo</creatorcontrib><creatorcontrib>Camacho, Aline Helen da Silva</creatorcontrib><creatorcontrib>Chimelli, Leila</creatorcontrib><creatorcontrib>Kasuki, Leandro</creatorcontrib><creatorcontrib>Lamback, Elisa B</creatorcontrib><creatorcontrib>Guterres, Alexandro</creatorcontrib><creatorcontrib>Gadelha, Monica R</creatorcontrib><title>miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.</description><subject>Acromegaly</subject><subject>Acromegaly - genetics</subject><subject>Adenoma</subject><subject>Biomarkers</subject><subject>Brain cancer</subject><subject>Disease control</subject><subject>Gene regulation</subject><subject>Health services</subject><subject>Humans</subject><subject>Insulin-like growth factors</subject><subject>Ligands</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - therapeutic use</subject><subject>miRNA</subject><subject>Pituitary gland</subject><subject>Post-transcription</subject><subject>Prediction models</subject><subject>Receptors, Somatostatin - genetics</subject><subject>Somatostatin</subject><subject>Statistical significance</subject><subject>Surgery</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUlrHDEQhYVJ8JpbzkGQSw7uWGtLfQkY4w0GEmznLDSa6omGbqkjaQK--pdb441xTqp6-vSo0kPoMyXfOe_IiV-NmQnCmVZyB-1TwVhDSKs-bNV76CDnFSGMM9ntoj3eqrajXbuPHkZ_03DNGzkd401NNbVPjQ2LV2FeBWwz_pVg4V2JKePY4xvIUwwZcIn4wqdcmksIkGzxMeDbONoSc6ldqKSDqT7DM7-sthlX7dSlOMLSDvdH6GNvhwyfXs5D9Pvi_O7sqpn9vLw-O501TlBWGmilo5Rz2UshgDGu1dw6oHoOVlnBeqH6ftE63QsJBLTmTthOuwo7JTjwQ_Tj2Xdaz0dYOAgl2cFMyY823ZtovXl_E_wfs4z_TNdRTXRbDb69GKT4dw25mNFnB8NgA8R1Nkwp2TIpNK3o1__QVVynUNfbUKKr4wtRqeNnqv5Fzgn6t2EoMZtwzXa4Ff-yvcAb_JomfwSDF59N</recordid><startdate>20230202</startdate><enddate>20230202</enddate><creator>Henriques, Daniel G</creator><creator>Miranda, Renan Lyra</creator><creator>Dezonne, Rômulo Sperduto</creator><creator>Wildemberg, Luiz Eduardo</creator><creator>Camacho, Aline Helen da Silva</creator><creator>Chimelli, Leila</creator><creator>Kasuki, Leandro</creator><creator>Lamback, Elisa B</creator><creator>Guterres, Alexandro</creator><creator>Gadelha, Monica R</creator><general>MDPI AG</general><general>MDPI</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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5838-0881</orcidid><orcidid>https://orcid.org/0000-0003-1339-3192</orcidid><orcidid>https://orcid.org/0000-0001-9514-0986</orcidid><orcidid>https://orcid.org/0000-0001-8323-1477</orcidid></search><sort><creationdate>20230202</creationdate><title>miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly</title><author>Henriques, Daniel G ; Miranda, Renan Lyra ; Dezonne, Rômulo Sperduto ; Wildemberg, Luiz Eduardo ; Camacho, Aline Helen da Silva ; Chimelli, Leila ; Kasuki, Leandro ; Lamback, Elisa B ; Guterres, Alexandro ; Gadelha, Monica R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-e65c11335f544e22387bace18bea7a42f47ffd6c8f45e0e883c4a98c44ec743e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Acromegaly</topic><topic>Acromegaly - genetics</topic><topic>Adenoma</topic><topic>Biomarkers</topic><topic>Brain cancer</topic><topic>Disease control</topic><topic>Gene regulation</topic><topic>Health services</topic><topic>Humans</topic><topic>Insulin-like growth factors</topic><topic>Ligands</topic><topic>MicroRNAs</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - therapeutic use</topic><topic>miRNA</topic><topic>Pituitary gland</topic><topic>Post-transcription</topic><topic>Prediction models</topic><topic>Receptors, Somatostatin - genetics</topic><topic>Somatostatin</topic><topic>Statistical significance</topic><topic>Surgery</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Henriques, Daniel G</creatorcontrib><creatorcontrib>Miranda, Renan Lyra</creatorcontrib><creatorcontrib>Dezonne, Rômulo Sperduto</creatorcontrib><creatorcontrib>Wildemberg, Luiz Eduardo</creatorcontrib><creatorcontrib>Camacho, Aline Helen da Silva</creatorcontrib><creatorcontrib>Chimelli, Leila</creatorcontrib><creatorcontrib>Kasuki, Leandro</creatorcontrib><creatorcontrib>Lamback, Elisa B</creatorcontrib><creatorcontrib>Guterres, Alexandro</creatorcontrib><creatorcontrib>Gadelha, Monica R</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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 Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Henriques, Daniel G</au><au>Miranda, Renan Lyra</au><au>Dezonne, Rômulo Sperduto</au><au>Wildemberg, Luiz Eduardo</au><au>Camacho, Aline Helen da Silva</au><au>Chimelli, Leila</au><au>Kasuki, Leandro</au><au>Lamback, Elisa B</au><au>Guterres, Alexandro</au><au>Gadelha, Monica R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2023-02-02</date><risdate>2023</risdate><volume>24</volume><issue>3</issue><spage>2875</spage><pages>2875-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>36769196</pmid><doi>10.3390/ijms24032875</doi><orcidid>https://orcid.org/0000-0002-5838-0881</orcidid><orcidid>https://orcid.org/0000-0003-1339-3192</orcidid><orcidid>https://orcid.org/0000-0001-9514-0986</orcidid><orcidid>https://orcid.org/0000-0001-8323-1477</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Acromegaly Acromegaly - genetics Adenoma Biomarkers Brain cancer Disease control Gene regulation Health services Humans Insulin-like growth factors Ligands MicroRNAs MicroRNAs - genetics MicroRNAs - therapeutic use miRNA Pituitary gland Post-transcription Prediction models Receptors, Somatostatin - genetics Somatostatin Statistical significance Surgery Tumorigenesis Tumors |
| title | miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly |
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