Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab-Paclitaxel Therapy Outcomes in Advanced Gastric Cancer
Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity,...
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| Veröffentlicht in: | International journal of molecular sciences 2024-12, Vol.25 (24), p.13498 |
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| creator | Piccinno, Emanuele Schirizzi, Annalisa Scalavino, Viviana De Leonardis, Giampiero Donghia, Rossella Fantasia, Alessia Ricci, Angela Dalia Lotesoriere, Claudio Giannelli, Gianluigi Serino, Grazia D'Alessandro, Rosalba |
| description | Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37,
= 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes. |
| doi_str_mv | 10.3390/ijms252413498 |
| format | Article |
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= 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms252413498</identifier><identifier>PMID: 39769259</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adult ; Aged ; Analysis ; Angiogenesis ; Angiopoietin-2 - blood ; Angiopoietin-2 - genetics ; Antibodies, Monoclonal, Humanized - administration & dosage ; Antibodies, Monoclonal, Humanized - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological markers ; Biomarkers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Cancer ; Cancer patients ; Cancer therapies ; Care and treatment ; Chemotherapy ; Circulating MicroRNA - blood ; Development and progression ; Ethylenediaminetetraacetic acid ; Female ; Gastric cancer ; Gene Expression Regulation, Neoplastic - drug effects ; Genes ; Humans ; Immunotherapy ; Male ; Medical prognosis ; Metastasis ; MicroRNA ; MicroRNAs ; MicroRNAs - blood ; MicroRNAs - genetics ; Middle Aged ; Monoclonal antibodies ; Paclitaxel ; Paclitaxel - administration & dosage ; Paclitaxel - therapeutic use ; Patients ; Prognosis ; Ramucirumab ; Stomach cancer ; Stomach Neoplasms - blood ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Targeted cancer therapy ; Treatment Outcome</subject><ispartof>International journal of molecular sciences, 2024-12, Vol.25 (24), p.13498</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c313t-ab905265ea8ac7f971fd2d2cbbb30a2f8fbf47efc5b1d3a76dfc1175a529cf2a3</cites><orcidid>0000-0002-2971-0802 ; 0000-0001-9604-366X ; 0000-0002-0273-2825 ; 0000-0002-9140-673X ; 0000-0002-5140-8060 ; 0000-0002-7999-9739 ; 0000-0002-7988-1917</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39769259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Piccinno, Emanuele</creatorcontrib><creatorcontrib>Schirizzi, Annalisa</creatorcontrib><creatorcontrib>Scalavino, Viviana</creatorcontrib><creatorcontrib>De Leonardis, Giampiero</creatorcontrib><creatorcontrib>Donghia, Rossella</creatorcontrib><creatorcontrib>Fantasia, Alessia</creatorcontrib><creatorcontrib>Ricci, Angela Dalia</creatorcontrib><creatorcontrib>Lotesoriere, Claudio</creatorcontrib><creatorcontrib>Giannelli, Gianluigi</creatorcontrib><creatorcontrib>Serino, Grazia</creatorcontrib><creatorcontrib>D'Alessandro, Rosalba</creatorcontrib><title>Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab-Paclitaxel Therapy Outcomes in Advanced Gastric Cancer</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Angiogenesis inhibition treatments are limited and are often too late for advanced gastric cancer (GC) patients, in whom its efficacy is reduced. New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37,
= 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.</description><subject>Adult</subject><subject>Aged</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Angiopoietin-2 - blood</subject><subject>Angiopoietin-2 - genetics</subject><subject>Antibodies, Monoclonal, Humanized - administration & dosage</subject><subject>Antibodies, Monoclonal, Humanized - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological markers</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Chemotherapy</subject><subject>Circulating MicroRNA - blood</subject><subject>Development and progression</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Gene Expression Regulation, Neoplastic - 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New molecular biomarkers are needed to optimize therapy regimens. In regard to this framework, circulating miRNAs, with high sensitivity and specificity, could be useful biomarkers of GC. The present longitudinal study was focused on analyzing the expression levels of a blood miRNA signature in a cohort of 40 patients receiving second-line therapy combining Ramucirumab and Paclitaxel, stratified based on their Progression-Free Survival (PFS). Using differential and bioinformatic analysis, miR-205-5p, miR-30e-3p, and miR-23b-3p were selected as possible predictive biomarkers, with the results showing that they were more highly expressed in patients exhibiting longer PFS and that they were involved in modulating angiogenesis. Furthermore, patients with longer PFS showed a progressive and significant decrease in the selected miRNA to minimal levels. The loss of the protective effect and the increased expression of the hypothetical targets, including angiopoietin-2, were then observed. The hypothesis was supported by the inverse correlation found for miR-205-5p and angiopoietin-2. Circulating levels of miR-205-5p were protective (HR = 0.37,
= 0.02) and patients with higher baseline miRNA levels had longer OS (12.47 vs. 9.00 months). Our findings suggest that these three miRNAs may be novel candidates as non-invasive predictive markers of therapy outcomes.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39769259</pmid><doi>10.3390/ijms252413498</doi><orcidid>https://orcid.org/0000-0002-2971-0802</orcidid><orcidid>https://orcid.org/0000-0001-9604-366X</orcidid><orcidid>https://orcid.org/0000-0002-0273-2825</orcidid><orcidid>https://orcid.org/0000-0002-9140-673X</orcidid><orcidid>https://orcid.org/0000-0002-5140-8060</orcidid><orcidid>https://orcid.org/0000-0002-7999-9739</orcidid><orcidid>https://orcid.org/0000-0002-7988-1917</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2024-12, Vol.25 (24), p.13498 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Adult Aged Analysis Angiogenesis Angiopoietin-2 - blood Angiopoietin-2 - genetics Antibodies, Monoclonal, Humanized - administration & dosage Antibodies, Monoclonal, Humanized - therapeutic use Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological markers Biomarkers Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Cancer Cancer patients Cancer therapies Care and treatment Chemotherapy Circulating MicroRNA - blood Development and progression Ethylenediaminetetraacetic acid Female Gastric cancer Gene Expression Regulation, Neoplastic - drug effects Genes Humans Immunotherapy Male Medical prognosis Metastasis MicroRNA MicroRNAs MicroRNAs - blood MicroRNAs - genetics Middle Aged Monoclonal antibodies Paclitaxel Paclitaxel - administration & dosage Paclitaxel - therapeutic use Patients Prognosis Ramucirumab Stomach cancer Stomach Neoplasms - blood Stomach Neoplasms - drug therapy Stomach Neoplasms - genetics Stomach Neoplasms - pathology Targeted cancer therapy Treatment Outcome |
| title | Circulating miR-23b-3p, miR-30e-3p, and miR-205-5p as Novel Predictive Biomarkers for Ramucirumab-Paclitaxel Therapy Outcomes in Advanced Gastric Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T00%3A04%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Circulating%20miR-23b-3p,%20miR-30e-3p,%20and%20miR-205-5p%20as%20Novel%20Predictive%20Biomarkers%20for%20Ramucirumab-Paclitaxel%20Therapy%20Outcomes%20in%20Advanced%20Gastric%20Cancer&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Piccinno,%20Emanuele&rft.date=2024-12-17&rft.volume=25&rft.issue=24&rft.spage=13498&rft.pages=13498-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms252413498&rft_dat=%3Cgale_proqu%3EA821834630%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3149648267&rft_id=info:pmid/39769259&rft_galeid=A821834630&rfr_iscdi=true |