Identification of BRD7 by whole-exome sequencing as a predictor for intermediate-stage hepatocellular carcinoma in patients undergoing TACE

J Cancer Res Clin Oncol. 2023 Oct;149(13):11247-11261. doi: 10.1007/s00432-023-04883-z. Epub 2023 Jun 26.

Abstract

Objective: In the present study, we aimed to identify potential predictors of intermediate-stage hepatocellular carcinoma (HCC) using whole-exome sequencing (WES) in patients undergoing transarterial chemoembolization (TACE).

Materials and methods: In A total of 51 patients, newly diagnosed with intermediate-stage HCC between January 2013 and December 2020, were enrolled. Prior to treatment, histological samples were collected for western blotting and immunohistochemistry. The predictive roles of clinical indicators and genes in patient prognosis were analyzed using univariate and multivariate analyses. Finally, the correlation between imaging features and gene signatures was examined.

Results: Using WES, we identified that bromodomain-containing protein 7 (BRD7) was significantly mutated in patients with different TACE responses. No significant difference in BRD7 expression was observed between patients with and without BRD7 mutations. HCC tumors exhibited higher BRD7 than normal liver tissues. Multivariate analysis revealed that alpha-fetoprotein (AFP), BRD7 expression, and BRD7 mutations were independent risk factors for progression-free survival (PFS). In addition, Child-Pugh class, BRD7 expression, and BRD7 mutations were independent risk factors for overall survival (OS). Patients with wild-type BRD7 and high BRD7 expression had worse PFS and OS, whereas those with mutated BRD7 and low BRD7 expression exhibited the best PFS and OS. The Kruskal-Wallis test revealed that wash-in enhancement on computed tomography might be an independent risk factor for high BRD7 expression.

Conclusion: BRD7 expression may be an independent risk factor for prognosis in patients with HCC undergoing TACE. Imaging features such as wash-in enhancement are closely related to BRD7 expression.

Keywords: BRD7; Hepatocellular carcinoma; Overall survival; Progression-free survival; Whole-exome sequencing.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic* / methods
  • Chromosomal Proteins, Non-Histone
  • Exome Sequencing
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / therapy
  • Prognosis
  • Retrospective Studies
  • Transcription Factors / genetics
  • Treatment Outcome

Substances

  • Transcription Factors
  • BRD7 protein, human
  • Chromosomal Proteins, Non-Histone