Division of Digestive Diseases and Nutrition, Section of HepatologyRush UniversityChicagoIllinoisUSA.
Department of Cellular & Molecular ResearchNational Cancer Center SingaporeSingapore.
Hepatol Commun. 2022 Nov;6(11):3247-3259. doi: 10.1002/hep4.2079. Epub 2022 Sep 12.
Transarterial chemoembolization (TACE) and transarterial radioembolization (TARE) treatment to hepatocellular carcinoma (HCC) are effective tools to control tumor growth, prolong survival, palliate symptoms, and improve quality of life for patients with intermediate-stage HCC. Nevertheless, there is high variability of local HCC responses to locoregional therapies; therefore, better and personalized prediction of tumor response to TACE is necessary for management of patients with HCC, especially when these modalities of treatment are used to bridge patients for liver transplant. Here, we investigated differential expression of hepatic cancer stem cell and hypoxia in residual HCC after TACE treatment in comparison with TARE. A publicly available gene data set was screened for differentially expressed genes (DEGs) in TACE_Response compared with TACE_Non-response HCC. Analysis of the GSE104580 data set displayed a total of 406 DEGs, including 196 down-regulated and 210 up-regulated DEGs. Of the 196 down-regulated DEGs, three hepatic cancer stem cell (CSC) markers and 11 hypoxia-related genes were identified. Immunohistochemical staining of hepatic CSC and hypoxia markers on explant liver tissues exhibited more intense positive staining of hepatic CSC markers (CD24, EpCAM) and hypoxia marker carbonic anhydrase 9 (CA9) in residual tumor nodule from patients with HCC treated with TACE compared with nontreated patients. Furthermore, Pearson's correlation analysis revealed the significant correlation between hepatic CSC markers and hypoxia marker, CA9. Conclusion: Hepatic CSC and hypoxia markers predict nonresponse to TACE and are differentially expressed in residual tumor after TACE compared with TARE. In the long term, TACE-induced hypoxia may select an aggressive HCC phenotype.
经导管动脉化疗栓塞术（TACE）和经导管动脉放射栓塞术（TARE）是控制肿瘤生长、延长生存时间、缓解症状和提高中晚期肝癌患者生活质量的有效手段。然而，局部肝癌对局部治疗的反应存在很大的变异性；因此，更好地预测 TACE 对肿瘤的反应，对肝癌患者的管理是必要的，尤其是当这些治疗方法用于为肝移植患者搭桥时。在这里，我们研究了 TACE 治疗后残留 HCC 中肝癌干细胞和缺氧的差异表达，与 TARE 相比。筛选了一个公开的基因数据集，以比较 TACE_Response 与 TACE_Non-response HCC 之间差异表达的基因（DEGs）。对 GSE104580 数据集的分析显示，共有 406 个 DEGs，包括 196 个下调和 210 个上调的 DEGs。在 196 个下调的 DEGs 中，鉴定出了三个肝癌干细胞（CSC）标记物和 11 个与缺氧相关的基因。对 TACE 治疗的 HCC 患者和未治疗患者的肝组织标本进行肝 CSC 和缺氧标志物的免疫组织化学染色显示，TACE 治疗后的残留肿瘤结节中肝 CSC 标志物（CD24、EpCAM）和缺氧标志物碳酸酐酶 9（CA9）的阳性染色更强。此外，Pearson 相关性分析显示，肝 CSC 标志物与缺氧标志物 CA9 之间存在显著相关性。结论：肝 CSC 和缺氧标志物可预测 TACE 无反应，并在 TACE 后残留肿瘤中与 TARE 相比差异表达。从长远来看，TACE 诱导的缺氧可能会选择侵袭性 HCC 表型。
