2026-08-29T14:12:19Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/183062024-02-19T15:26:48Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927col_20.500.12105_16978col_20.500.12105_16982col_20.500.12105_16988col_20.500.12105_16989
Repisalud author Conde, Elisa author Earl, Julie author Crespo-Toro, Lorena author Blanco-Agudo, Carolina author Ramos-Muñoz, Edurne author Rodríguez-Serrano, E Macarena author Martínez Ávila, Jose Carlos author Salinas-Muñoz, Laura author Serrano-Huertas, Silvia author Ferreiro, Reyes author Rodriguez-Garrote, Mercedes author Sainz, Bruno author Massuti, Bartomeu author Alfonso, Pilar García author Benavides, Manuel author Aranda, Enrique author García-Bermejo, María Laura author Carrato, Alfredo 2024-02-19T15:26:48Z 2024-02-19T15:26:48Z 2021-04-04 10.3390/cancers13071710 2072-6694 Cancers http://hdl.handle.net/10668/17660 33916610 http://hdl.handle.net/20.500.12105/18306 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. eng biomarkers colorectal cancer miRNAs regorafenib toxicity treatment response Biomarkers Associated with Regorafenib First-Line Treatment Benefits in Metastatic Colorectal Cancer Patients: REFRAME Molecular Study. research article