Department of Interventional Oncology, The First Affiliated Hospital of Sun Yat-Sen University, No. 58 Zhongshan 2 Road, Guangzhou, 510080, Guangdong, People's Republic of China.
Department of Radiology, Guizhou Provincial People's Hospital, No. 83 East Zhongshan Road, Guiyang, 550002, Guizhou, China.
J Cancer Res Clin Oncol. 2023 Oct;149(13):11247-11261. doi: 10.1007/s00432-023-04883-z. Epub 2023 Jun 26.
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).
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.
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.
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.
本研究旨在通过对接受经动脉化疗栓塞术(TACE)的患者进行全外显子组测序(WES),确定中晚期肝细胞癌(HCC)的潜在预测因子。
共纳入 51 例 2013 年 1 月至 2020 年 12 月新诊断为中晚期 HCC 的患者。治疗前采集组织学样本进行 Western blot 和免疫组化分析。采用单因素和多因素分析方法分析临床指标和基因对患者预后的预测作用。最后,还检查了影像学特征与基因特征之间的相关性。
通过 WES,我们发现 BRD7 在不同 TACE 反应患者中存在显著突变。BRD7 突变患者与无 BRD7 突变患者的 BRD7 表达无显著差异。HCC 肿瘤的 BRD7 表达高于正常肝组织。多因素分析显示,甲胎蛋白(AFP)、BRD7 表达和 BRD7 突变是无进展生存期(PFS)的独立危险因素。此外,Child-Pugh 分级、BRD7 表达和 BRD7 突变是总生存期(OS)的独立危险因素。BRD7 野生型且高表达的患者 PFS 和 OS 较差,而 BRD7 突变且低表达的患者 PFS 和 OS 最佳。Kruskal-Wallis 检验显示 CT 增强的动脉期增强可能是 BRD7 高表达的独立危险因素。
BRD7 表达可能是 TACE 治疗 HCC 患者预后的独立危险因素。影像学特征如动脉期增强与 BRD7 表达密切相关。