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Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma
Giannitrapani, Lydia Di Gaudio, Francesca Cervello, Melchiorre Scionti, Francesca Ciliberto, Domenico Staropoli, Nicoletta Agapito, Giuseppe Cannataro, Mario Tassone, Pierfrancesco Tagliaferri, Pierosandro
Giannitrapani, Lydia
Di Gaudio, Francesca
Cervello, Melchiorre
Scionti, Francesca
Ciliberto, Domenico
Staropoli, Nicoletta
Agapito, Giuseppe
Cannataro, Mario
Tassone, Pierfrancesco
Tagliaferri, Pierosandro
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2024-02-12
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https://doi.org/10.3390/ijms25042197
Abstract
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.
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Giannitrapani, L.; Di Gaudio, F.; Cervello, M.; Scionti, F.; Ciliberto, D.; Staropoli, N.; Agapito, G.; Cannataro, M.; Tassone, P.; Tagliaferri, P.; et al. Genetic Biomarkers of Sorafenib Response in Patients with Hepatocellular Carcinoma. Int. J. Mol. Sci. 2024, 25, 2197. https://doi.org/10.3390/ijms25042197
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International Journal of Molecular Sciences, Vol. 25, Iss. 4
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