Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study
First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (S...
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| Veröffentlicht in: | Cancers 2021-04, Vol.13 (7), p.1710 |
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| creator | Conde, Elisa Earl, Julie Crespo-Toro, Lorena Blanco-Agudo, Carolina Ramos-Muñoz, Edurne Rodríguez-Serrano, E Macarena Martínez Ávila, Jose Carlos Salinas-Muñoz, Laura Serrano-Huertas, Silvia Ferreiro, Reyes Rodriguez-Garrote, Mercedes Sainz, Jr, Bruno Massuti, Bartomeu Alfonso, Pilar García Benavides, Manuel Aranda, Enrique García-Bermejo, María Laura Carrato, Alfredo |
| description | First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment. |
| doi_str_mv | 10.3390/cancers13071710 |
| format | Article |
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To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13071710</identifier><identifier>PMID: 33916610</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiogenesis ; Asthenia ; Biomarkers ; Biopsy ; Cancer ; Cancer therapies ; Colorectal cancer ; Colorectal carcinoma ; Genotyping ; Homeostasis ; Kinases ; Metastases ; Metastasis ; MicroRNAs ; miRNA ; Notch1 protein ; Patients ; Peritoneum ; Serum levels ; Single-nucleotide polymorphism ; Toxicity ; Tumors ; Vascular endothelial growth factor ; Vascular endothelial growth factor receptors</subject><ispartof>Cancers, 2021-04, Vol.13 (7), p.1710</ispartof><rights>2021 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>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-c0685326bc5be371961af4e8ca04c00dfae7552f59286a4aff8a8f3f7eb472c73</citedby><cites>FETCH-LOGICAL-c421t-c0685326bc5be371961af4e8ca04c00dfae7552f59286a4aff8a8f3f7eb472c73</cites><orcidid>0000-0002-8167-2276 ; 0000-0002-4373-9978 ; 0000-0001-7749-8140 ; 0000-0001-9360-4716 ; 0000-0002-3751-9602 ; 0000-0002-9817-1291</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/PMC8038427/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038427/$$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/33916610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Conde, Elisa</creatorcontrib><creatorcontrib>Earl, Julie</creatorcontrib><creatorcontrib>Crespo-Toro, Lorena</creatorcontrib><creatorcontrib>Blanco-Agudo, Carolina</creatorcontrib><creatorcontrib>Ramos-Muñoz, Edurne</creatorcontrib><creatorcontrib>Rodríguez-Serrano, E Macarena</creatorcontrib><creatorcontrib>Martínez Ávila, Jose Carlos</creatorcontrib><creatorcontrib>Salinas-Muñoz, Laura</creatorcontrib><creatorcontrib>Serrano-Huertas, Silvia</creatorcontrib><creatorcontrib>Ferreiro, Reyes</creatorcontrib><creatorcontrib>Rodriguez-Garrote, Mercedes</creatorcontrib><creatorcontrib>Sainz, Jr, Bruno</creatorcontrib><creatorcontrib>Massuti, Bartomeu</creatorcontrib><creatorcontrib>Alfonso, Pilar García</creatorcontrib><creatorcontrib>Benavides, Manuel</creatorcontrib><creatorcontrib>Aranda, Enrique</creatorcontrib><creatorcontrib>García-Bermejo, María Laura</creatorcontrib><creatorcontrib>Carrato, Alfredo</creatorcontrib><title>Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. In conclusion, VEGF and VEGFR SNPs, miRNAs, and Notch 1 levels are potential useful biomarkers for the management of advanced CRC under regorafenib treatment.</description><subject>Angiogenesis</subject><subject>Asthenia</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Genotyping</subject><subject>Homeostasis</subject><subject>Kinases</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Notch1 protein</subject><subject>Patients</subject><subject>Peritoneum</subject><subject>Serum levels</subject><subject>Single-nucleotide polymorphism</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular endothelial growth factor 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Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study</title><author>Conde, Elisa ; Earl, Julie ; Crespo-Toro, Lorena ; Blanco-Agudo, Carolina ; Ramos-Muñoz, Edurne ; Rodríguez-Serrano, E Macarena ; Martínez Ávila, Jose Carlos ; Salinas-Muñoz, Laura ; Serrano-Huertas, Silvia ; Ferreiro, Reyes ; Rodriguez-Garrote, Mercedes ; Sainz, Jr, Bruno ; Massuti, Bartomeu ; Alfonso, Pilar García ; Benavides, Manuel ; Aranda, Enrique ; García-Bermejo, María Laura ; Carrato, Alfredo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-c0685326bc5be371961af4e8ca04c00dfae7552f59286a4aff8a8f3f7eb472c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Asthenia</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Genotyping</topic><topic>Homeostasis</topic><topic>Kinases</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>Notch1 protein</topic><topic>Patients</topic><topic>Peritoneum</topic><topic>Serum levels</topic><topic>Single-nucleotide polymorphism</topic><topic>Toxicity</topic><topic>Tumors</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular endothelial growth factor receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Conde, Elisa</creatorcontrib><creatorcontrib>Earl, Julie</creatorcontrib><creatorcontrib>Crespo-Toro, Lorena</creatorcontrib><creatorcontrib>Blanco-Agudo, Carolina</creatorcontrib><creatorcontrib>Ramos-Muñoz, Edurne</creatorcontrib><creatorcontrib>Rodríguez-Serrano, E Macarena</creatorcontrib><creatorcontrib>Martínez Ávila, Jose Carlos</creatorcontrib><creatorcontrib>Salinas-Muñoz, 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Alfredo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2021-04-04</date><risdate>2021</risdate><volume>13</volume><issue>7</issue><spage>1710</spage><pages>1710-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>First-line treatment with regorafenib in frail metastatic colorectal cancer (mCRC) patients has shown some benefit. To accurately identify such patients before treatment, we studied blood biomarkers and primary tumor molecules. We unveiled serum microRNAs (miRNAs), single-nucleotide polymorphisms (SNPs) in angiogenic-related genes, and Notch 1 expression as biomarkers associated with response or toxicity. MicroRNA array profiling and genotyping of selected SNPs were performed in the blood of fragile mCRC patients treated with regorafenib. Notch 1 and CRC-associated miRNA expression was also analyzed in tumors. High levels of miR-185-5p in serum, rs7993418 in the vascular endothelial growth factor receptor 1 (VEGFR1) gene, and Notch 1 expression in biopsies were associated with a favorable response to treatment. Serum levels of miR-126-3p and miR-152-3p and tumor expression of miR-92a-1-5p were associated with treatment toxicity, particularly interesting in patients exhibiting comorbidities, and high levels of miR-362-3p were associated with asthenia. Additionally, several miRNAs were associated with the presence of metastasis, local recurrence, and peritoneal metastasis. Besides, miRNAs determined in primary tumors were associated with tumor-node-metastasis (TNM) staging. The rs2305948 and rs699947 SNPs in VEGFR2 and VEGFA, respectively, were markers of poor prognosis correlating with locoregional relapse, a higher N stage, and metastatic shedding. 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| source | MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central; PubMed Central Open Access |
| subjects | Angiogenesis Asthenia Biomarkers Biopsy Cancer Cancer therapies Colorectal cancer Colorectal carcinoma Genotyping Homeostasis Kinases Metastases Metastasis MicroRNAs miRNA Notch1 protein Patients Peritoneum Serum levels Single-nucleotide polymorphism Toxicity Tumors Vascular endothelial growth factor Vascular endothelial growth factor receptors |
| title | Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study |
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