Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.
Differential expression of hepatic cancer stemness and hypoxia markers in residual cancer after locoregional therapies for hepatocellular carcinoma.
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肝细胞癌局部疗法后，残留癌症中肝癌干和缺氧标记的差异表达。
DOI：
10.1002/hep4.2079
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发表时间：
2022-11
影响因子：
5.1
通讯作者：
中科院分区：
文献类型：
--
作者：
经动脉化疗栓塞（TACE）和经动脉放射栓塞（TARE）治疗肝细胞癌（HCC）是控制肿瘤生长、延长生存期、缓解症状和改善中期HCC患者生活质量的有效工具。然而，局部HCC对局部治疗的反应存在高度可变性；因此，更好和个性化的预测肿瘤对TACE的反应对于HCC患者的治疗是必要的，特别是当这些治疗方式被用来为肝移植患者搭建桥梁时。在这里，我们研究了TACE治疗与TARE治疗后残余HCC中肝癌干细胞和缺氧的差异表达。一个公开可用的基因数据集筛选TACE_Response与TACE_Non - response HCC中的差异表达基因（DEGs）。对GSE104580数据集的分析显示，共有406个基因位点，其中196个下调，210个上调。在196个下调的deg中，鉴定出3个肝癌干细胞（CSC）标记和11个缺氧相关基因。肝细胞癌患者经TACE治疗后残余肿瘤结节中肝CSC标志物（CD24、EpCAM）和缺氧标志物碳酸酐酶9 （CA9）的免疫组化染色较未接受TACE治疗的患者更为强烈。此外，Pearson相关分析显示，肝CSC标志物与缺氧标志物CA9之间存在显著相关性。结论：与TARE相比，肝CSC和缺氧标志物预测TACE无反应，并且在TACE后残余肿瘤中表达差异。从长期来看，TACE诱导的缺氧可能会选择侵袭性HCC表型。来自TACE_Non - response/ response患者的肝活检转录分析以及移植肝组织、肝CSC和缺氧标志物的免疫组化预测TACE无反应，并且与TARE相比，TACE后残余肿瘤中的表达增加。与TARE相比，TACE诱导的缺氧可选择侵袭性HCC表型。
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. Transcriptom analysis of liver biopsies from TACE_Non‐response/Response patients and IHC on explant liver tissues, hepatic CSC and hypoxia markers predict non‐response to TACE and have increased expression in residual tumor after TACE compared with TARE. TACE‐induced hypoxia may select an aggressive HCC phenotype when compared with TARE.
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影响因子：
3.8
作者：
Fan L;He F;Liu H;Zhu J;Liu Y;Yin Z;Wang L;Guo Y;Wang Z;Yan Q;Huang G
通讯作者：
Huang G
影响因子：
6.6
作者：
Rhee, Hyungjin;Chung, Taek;Park, Young Nyun
通讯作者：
Park, Young Nyun
影响因子：
11.2
作者：
Hwang, Rosa F.;Moore, Todd;Logsdon, Craig D.
通讯作者：
Logsdon, Craig D.
影响因子：
9.2
作者：
Fako, Valerie;Martin, Sean P.;Wang, Xin Wei
通讯作者：
Wang, Xin Wei
影响因子：
29.4
作者：
Ma, Stephanie;Chan, Kwok-Wah;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan