Hepatocellular carcinoma after a sustained virological response by direct-acting antivirals harbors TP53 inactivation.
direct-acting antiviral agent
hepatitis C virus
hepatocellular carcinoma
interferon
sustained virological response
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
01
12
2021
received:
15
09
2021
accepted:
15
12
2021
pubmed:
18
2
2022
medline:
29
4
2022
entrez:
17
2
2022
Statut:
ppublish
Résumé
The genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood. Sixty-nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole-exome sequencing. Among the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV-positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV-SVR. According to the HCV treatment, 35 HCV-SVR HCCs were classified into two groups: eight tumors with DAA (HCV-SVR-DAA) and 24 tumors with interferon (HCV-SVR-IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV-SVR than in HCV-positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV-SVR samples than in HCV-positive samples (p = 0.048). Among the patients with HCV-SVR, the frequency of samples with TP53 mutations was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors (p = 0.030). TP53 inactivation scores in HCV-SVR-DAA tumors were found to be significantly enhanced in comparison to HCV-SVR-IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV-SVR-DAA tumors. HCV-SVR-DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV-SVR-IFN. Our dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors.
Identifiants
pubmed: 35174643
doi: 10.1002/cam4.4571
pmc: PMC9041076
doi:
Substances chimiques
Antiviral Agents
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
Interferons
9008-11-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1769-1786Informations de copyright
© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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