Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Surgery, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2021 Dec;44(6 Suppl 1):S73-S83. doi: 10.1016/j.bj.2020.07.001. Epub 2020 Jul 15.
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.
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.
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).
Higher percentage genome change and amplification of chromosome 7q in advanced HCC is associated with sorafenib resistance.
肝细胞癌 (HCC) 可能源于基因组不稳定性，且预后较差。索拉非尼是晚期 HCC 的一线治疗药物，但治疗效果不足 50%。需要生物标志物来预测晚期 HCC 患者接受索拉非尼治疗的疗效。在此，我们评估了接受索拉非尼治疗的晚期 HCC 患者的染色体拷贝数异常 (CNA) 与药物反应的关系。
对 23 例接受部分肝切除后出现晚期复发的 HCC 患者的索拉非尼治疗反应进行分析，采用改良的实体瘤反应评价标准 (mRECIST)。对肿瘤切除后获得的福尔马林固定石蜡包埋 (FFPE) 组织标本进行分析，采用 Affymetrix OncoScan® FFPE 检测。
在本研究分析的 23 例患者中，7 例 (30.4%) 对索拉非尼有完全/部分缓解 (CR/PR)，7 例 (30.4%) 病情稳定 (SD)，9 例 (39.1%) 病情进展 (PD)。CR/PR/SD 患者的全基因组经 OncoScan 平台获得的基因组改变百分比平均值为 19.8%，而 PD 组为 50.02%（p=0.055）。在进展时间分析中，基因组改变百分比高于 33%与索拉非尼治疗的不良预后相关 (p=0.007)，与总生存时间相关 (p=0.096)。在这些 CNA 中，7q 染色体扩增，包含多药耐药基因 ATP 结合盒亚家族 B 成员 1 (ACBC1)，与较差的总生存率显著相关 (p=0.004) 和进展时间相关 (p<0.001)。
晚期 HCC 中较高的基因组改变百分比和 7q 染色体扩增与索拉非尼耐药相关。
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