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Prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma under systemic treatment.
Sogbe, Miguel; Bilbao, Idoia; Marchese, Francesco P; Zazpe, Jon; De Vito, Annarosaria; Pozuelo, Marta; D'Avola, Delia; Iñarrairaegui, Mercedes; Berasain, Carmen; Arechederra, Maria; Argemi, Josepmaria; Sangro, Bruno.
Afiliação
  • Sogbe M; Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain.
  • Bilbao I; Clinica Universidad de Navarra, Liver Unit, Pamplona, Spain.
  • Marchese FP; University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain.
  • Zazpe J; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  • De Vito A; University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain.
  • Pozuelo M; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  • D'Avola D; University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain.
  • Iñarrairaegui M; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  • Berasain C; University of Navarra, Center for Applied Medical Research (CIMA), Computational Biology and Translational Genomics Program, Pamplona, Spain.
  • Arechederra M; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.
  • Argemi J; Clinica Universidad de Navarra, Internal Medicine Department, Madrid, Spain.
  • Sangro B; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Pamplona, Spain.
Clin Mol Hepatol ; 30(2): 177-190, 2024 Apr.
Article em En | MEDLINE | ID: mdl-38163441
ABSTRACT
BACKGROUND/

AIMS:

New prognostic markers are needed to identify patients with hepatocellular carcinoma (HCC) who carry a worse prognosis. Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5× coverage) of cell-free DNA (cfDNA) has emerged as a low-cost promising tool to assess both circulating tumor DNA (ctDNA) fraction and large structural genomic alterations. Here, we studied the performance of ULP-WGS of plasma cfDNA to infer prognosis in patients with HCC.

METHODS:

Plasma samples were obtained from patients with HCC prior to surgery, locoregional or systemic therapy, and were analyzed by ULP-WGS of cfDNA to an average genome-wide fold coverage of 0.3x. ctDNA and copy number alterations (CNA) were estimated using the software package ichorCNA.

RESULTS:

Samples were obtained from 73 HCC patients at different BCLC stages (BCLC 0/A n=37, 50.7%; BCLC B/C n=36, 49.3%). ctDNA was detected in 18 out of 31 patients who received systemic treatment. Patients with detectable ctDNA showed significantly worse overall survival (median, 13.96 months vs not reached). ctDNA remained an independent predictor of prognosis after adjustment by clinical-pathologic features and type of systemic treatment (hazard ratio 7.69; 95%, CI 2.09-28.27). Among ctDNA-positive patients under systemic treatments, the loss of large genomic regions in 5q and 16q arms was associated with worse prognosis after multivariate analysis.

CONCLUSION:

ULP-WGS of cfDNA provides clinically relevant information about the tumor biology. The presence of ctDNA and the loss of 5q and 16q arms in ctDNA-positive patients are independent predictors of worse prognosis in patients with advanced HCC receiving systemic therapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Ácidos Nucleicos Livres / DNA Tumoral Circulante / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Clin Mol Hepatol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carcinoma Hepatocelular / Ácidos Nucleicos Livres / DNA Tumoral Circulante / Neoplasias Hepáticas Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Clin Mol Hepatol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Espanha