Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma.

Autor: Giannitrapani L; Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy.; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy., Di Gaudio F; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy., Cervello M; Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy., Scionti F; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy., Ciliberto D; Medical and Translational Oncology Unit, A.O.U. R. Dulbecco, 88100 Catanzaro, Italy., Staropoli N; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Medical and Translational Oncology Unit, A.O.U. R. Dulbecco, 88100 Catanzaro, Italy., Agapito G; Department of Legal, Economic and Social Sciences, Magna Graecia University, 88100 Catanzaro, Italy., Cannataro M; Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, 88100 Catanzaro, Italy., Tassone P; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Medical and Translational Oncology Unit, A.O.U. R. Dulbecco, 88100 Catanzaro, Italy.; College of Science and Technology, Temple University, Philadelphia, PA 19122, USA., Tagliaferri P; Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 Catanzaro, Italy.; Medical and Translational Oncology Unit, A.O.U. R. Dulbecco, 88100 Catanzaro, Italy., Seidita A; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy.; Villa Sofia-Cervello Hospital, C.O.U. Medical Oncology, 90146 Palermo, Italy., Soresi M; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy., Affronti M; Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy., Bertino G; Hepatology Unit, A.O.U. Policlinico-San Marco, Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy., Russello M; Liver Unit of ARNAS Garibaldi-Nesima, 95100 Catania, Italy., Ciriminna R; Institute of Nanostructured Materials, National Research Council (CNR), 90146 Palermo, Italy., Lino C; Institute of Nanostructured Materials, National Research Council (CNR), 90146 Palermo, Italy., Spinnato F; Villa Sofia-Cervello Hospital, C.O.U. Medical Oncology, 90146 Palermo, Italy., Verderame F; Villa Sofia-Cervello Hospital, C.O.U. Medical Oncology, 90146 Palermo, Italy., Augello G; Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy., Arbitrio M; Institute for Biomedical Research and Innovation, National Research Council (CNR), 88100 Catanzaro, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Feb 12; Vol. 25 (4). Date of Electronic Publication: 2024 Feb 12.
DOI: 10.3390/ijms25042197
Abstrakt: The identification of biomarkers for predicting inter-individual sorafenib response variability could allow hepatocellular carcinoma (HCC) patient stratification. SNPs in angiogenesis- and drug absorption, distribution, metabolism, and excretion (ADME)-related genes were evaluated to identify new potential predictive biomarkers of sorafenib response in HCC patients. Five known SNPs in angiogenesis-related genes, including VEGF-A , VEGF-C , HIF-1a , ANGPT2 , and NOS3 , were investigated in 34 HCC patients (9 sorafenib responders and 25 non-responders). A subgroup of 23 patients was genotyped for SNPs in ADME genes. A machine learning classifier method was used to discover classification rules for our dataset. We found that only the VEGF-A (rs2010963) C allele and CC genotype were significantly associated with sorafenib response. ADME-related gene analysis identified 10 polymorphic variants in ADH1A (rs6811453), ADH6 (rs10008281), SULT1A2/CCDC101 (rs11401), CYP26A1 (rs7905939), DPYD (rs2297595 and rs1801265), FMO2 (rs2020863), and SLC22A14 (rs149738, rs171248, and rs183574) significantly associated with sorafenib response. We have identified a genetic signature of predictive response that could permit non-responder/responder patient stratification. Angiogenesis- and ADME-related genes correlation was confirmed by cumulative genetic risk score and network and pathway enrichment analysis. Our findings provide a proof of concept that needs further validation in follow-up studies for HCC patient stratification for sorafenib prescription.
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje