1. Ultra Deep Sequencing of Circulating Cell-Free DNA as a Potential Tool for Hepatocellular Carcinoma Management
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Mónica Higuera, Elena Vargas-Accarino, María Torrens, Josep Gregori, María Teresa Salcedo, Joan Martínez-Campreciós, Gloria Torres, María Bermúdez-Ramos, Itxarone Bilbao, Mercedes Guerrero-Murillo, Xavier Serres-Créixams, Xavier Merino, Francisco Rodríguez-Frías, Josep Quer, Beatriz Mínguez, Institut Català de la Salut, [Higuera M, Torrens M, Torres G] Grup de Recerca en Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Vargas-Accarino E, Martínez-Campreciós J] Grup de Recerca en Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Gregori J] Grup de Recerca en Hepatitis Viral, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [Salcedo MT] Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Servei d’Anatomia Patològica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain. [Bermúdez-Ramos M] Grup de Recerca en Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [Bilbao I] Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Servei de Cirurgia Hepatobiliopancreàtica i Trasplantaments, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Guerrero-Murillo M] Grup de Recerca en Hepatitis Viral, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Serres-Créixams X, Merino X] Servei de Radiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Rodríguez-Frías F] Servei de Bioquímica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Quer J] Grup de Recerca en Hepatitis Viral, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Mínguez B] Grup de Recerca en Malalties Hepàtiques, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Unitat Hepàtica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Cancer Research ,técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,liquid biopsy ,cfDNA ,HCC ,biomarkers ,neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias hepáticas::carcinoma hepatocelular [ENFERMEDADES] ,Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::Cell-Free Nucleic Acids [CHEMICALS AND DRUGS] ,Other subheadings::/therapy [Other subheadings] ,Fetge - Càncer - Aspectes genètics ,Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, DNA [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,Fetge - Càncer - Tractament ,Àcids nucleics - Anàlisi ,Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms::Carcinoma, Hepatocellular [DISEASES] ,nucleótidos y nucleósidos de ácidos nucleicos::ácidos nucleicos::ácidos nucleicos libres de células [COMPUESTOS QUÍMICOS Y DROGAS] ,Oncology ,Otros calificadores::/terapia [Otros calificadores] - Abstract
Biomarkers; cfDNA; Liquid biopsy Biomarcadores; cfDNA; Biopsia líquida Biomarcadors; cfDNA; Biòpsia líquida Background: Cell-free DNA (cfDNA) concentrations have been described to be inversely correlated with prognosis in cancer. Mutations in HCC-associated driver genes in cfDNA have been reported, but their relation with patient’s outcome has not been described. Our aim was to elucidate whether mutations found in cfDNA could be representative from those present in HCC tissue, providing the rationale to use the cfDNA to monitor HCC. Methods: Tumoral tissue, paired nontumor adjacent tissue and blood samples were collected from 30 HCC patients undergoing curative therapies. Deep sequencing targeting HCC driver genes was performed. Results: Patients with more than 2 ng/µL of cfDNA at diagnosis had higher mortality (mean OS 24.6 vs. 31.87 months, p = 0.01) (AUC = 0.782). Subjects who died during follow-up, had a significantly higher number of mutated genes (p = 0.015) and number of mutations (p = 0.015) on cfDNA. Number of mutated genes (p = 0.001), detected mutations (p = 0.001) in cfDNA and ratio (number of mutations/cfDNA) (p = 0.003) were significantly associated with recurrence. However, patients with a ratio (number of mutations/cfDNA) above 6 (long-rank p = 0.0003) presented a higher risk of recurrence than those with a ratio under 6. Detection of more than four mutations in cfDNA correlated with higher risk of death (long-rank p = 0.042). Conclusions: In summary, cfDNA and detection of prevalent HCC mutations could have prognostic implications in early-stage HCC patients This research was funded by Instituto de Salud Carlos III (ISCIII) (PI18/00961) and (PI21/00714) to B.M. PI19/00301 by Instituto de Salud Carlos III (ISCIII) and Centro para el Desarrollo Tecnológico Industrial (CDTI) from the Spanish Ministry of Economy and Business, grant number IDI-20200297 to J.Q., E.V.-A. is a recipient of a predoctoral fellowship from Instituto de Salud Carlos III (ISCIII) (FI18/00027).
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- 2022
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