Percentage genome change and chromosome 7q amplification predict sorafenib response in advanced hepatocellular carcinoma

Ming Chin Yu, Tsung Han Wu, Chao Wei Lee, Yun Shien Lee, Jang Hau Lian, Chia Lung Tsai, Sen Yung Hsieh, Chi Neu Tsai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

2 Scopus citations

Abstract

Background: Hepatocellular carcinoma (HCC) may arise from genomic instability and has dismal outcome. Sorafenib is the first-line treatment for advanced stage HCC, but its therapeutic efficacy is less than 50%. Biomarkers for predicting the therapeutic efficacy of sorafenib administration to patients with advanced HCC are required. Here, we evaluated the role of chromosomal copy number aberrations (CNAs) in patients with advanced HCC who were treated with sorafenib along with their drug response. Methods: The response to sorafenib treatment of twenty-three HCC patients who developed advanced recurrence after partial hepatectomy was analyzed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Formalin fixed paraffin embedded (FFPE) tissue specimens obtained after tumor resection were analyzed using the Affymetrix OncoScan® FFPE assay. Results: From the 23 patients analyzed in this study, 7 (30.4%) had complete/partial response to sorafenib (CR/PR), 7 (30.4%) had stable disease (SD), and 9 (39.1%) had progressive disease (PD). The mean genome-wide percentage of genome change acquisition via the OncoScan platform was 19.8% for patients with CR/PR/SD and 50.02% in the PD group (p = 0.055). Percentage of genome change above 33% was associated with adverse outcomes for sorafenib treatment in the time-to-progression analysis (p = 0.007) and overall survival (p = 0.096). Among these CNAs, amplification of chromosome 7q, containing the multidrug resistance gene ATP Binding Cassette Subfamily B Member 1 (ACBC1), significantly associated with poor overall survival (p = 0.004) and time-to-progression (p < 0.001). Conclusions: Higher percentage genome change and amplification of chromosome 7q in advanced HCC is associated with sorafenib resistance.

Original languageEnglish
Pages (from-to)S73-S83
JournalBiomedical Journal
Volume44
Issue number6
DOIs
StatePublished - 12 2021

Bibliographical note

Publisher Copyright:
© 2020 Chang Gung University

Keywords

  • 7q amplification
  • ABCB1
  • Advanced HCC
  • Copy number aberrations
  • Sorafenib

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