Graduate Institute of Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Department of Hematology, School of Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar 14210, Mongolia.
Medicina (Kaunas). 2022 Feb 1;58(2):212. doi: 10.3390/medicina58020212.
: Activation of NRF2, a key transcription factor of cytoprotectant against oxidative stress, and its target genes are associated with aggressive tumor progression, metastasis and poor survival. In addition, NRF2 signaling mediates cancer stem cell (CSC)-like properties in hepatocellular carcinoma (HCC) cells. Moreover, CSCs have been associated with HCC onset and unfavorable prognosis. Transcatheter arterial embolization (TAE) and/or transcatheter arterial chemoembolization (TACE), which attempt to restrict blood supply to diminish tumor growth, can create a hypoxic environment. However, its effect on NRF2 signaling and CSC marker CD133 in the context of prognosis of HCCs have not been investigated. Therefore, we studied the possible role of the expressions of NRF2, its target genes and CSC markers CD133 and EpCAM on the survival of HCC patients after TAE/TACE. : RT-qPCR was performed with 120 tumor (T) and adjacent tumor (N) tissue pairs. Expression of a single marker or combination was assessed for associations with survival of HCC patients after TAE/TACE. : The result of multivariate Cox regression showed that vascular invasion (HR, 1.821; = 0.015), metastasis (HR, 2.033; = 0.049) and CD133 overexpression (HR, 2.013; = 0.006) were associated with poor survival. In a Kaplan-Meier survival analysis, patients with high expression of CD133 had shorter overall survival (OS) than those with low expression of CD133 in post-TAE/TACE HCC ( < 0.001). In contrast, neither NRF2 nor components of its signaling pathway correlated with survival. Combination marker analysis showed that co-expression of NQO1 and CD133 was associated with poor outcome. : This study suggests that analyzing the expression status of CD133 alone and co-expression of NQO1 and CD133 may have additional value in predicting the outcome of TAE/TACE-treated HCC patients.
: NRF2 是一种细胞保护因子，可对抗氧化应激，其激活及其靶基因与侵袭性肿瘤进展、转移和不良预后相关。此外，NRF2 信号转导可介导肝癌（HCC）细胞中的癌症干细胞（CSC）样特性。此外，CSC 与 HCC 的发生和不利预后有关。经导管动脉栓塞术（TAE）和/或经导管动脉化疗栓塞术（TACE）试图限制血液供应以减少肿瘤生长，可产生缺氧环境。然而，其对 HCC 预后中 NRF2 信号转导和 CSC 标志物 CD133 的影响尚未得到研究。因此，我们研究了 TAE/TACE 后 NRF2、其靶基因和 CSC 标志物 CD133 和 EpCAM 的表达对 HCC 患者生存的可能作用。 : 对 120 对肿瘤（T）和相邻肿瘤（N）组织进行了 RT-qPCR。评估单一标志物或组合的表达与 TAE/TACE 后 HCC 患者生存的相关性。 : 多变量 Cox 回归的结果表明，血管侵犯（HR，1.821； = 0.015）、转移（HR，2.033； = 0.049）和 CD133 过表达（HR，2.013； = 0.006）与不良预后相关。Kaplan-Meier 生存分析显示，TAE/TACE 后 HCC 中 CD133 高表达患者的总生存期（OS）短于 CD133 低表达患者（<0.001）。相比之下，NRF2 及其信号通路成分均与生存无关。组合标志物分析表明，NQO1 和 CD133 的共表达与不良预后相关。 : 本研究表明，分析 CD133 单独表达和 NQO1 与 CD133 共表达的状态可能对预测 TAE/TACE 治疗 HCC 患者的预后有额外的价值。
