Liu Da-Hua, Wen Gui-Min, Song Chang-Liang, Xu Ze-Jun, Ren Fu, Zhao Zhen-Ying, Xia Pu
Biological Anthropology Institute, College of Basic Medical Science, Jinzhou Medical University Jinzhou, Liaoning, P. R. China.
Department of Basic Nursing, College of Nursing, Jinzhou Medical University Jinzhou, Liaoning, P. R. China.
Am J Cancer Res. 2023 Mar 15;13(3):802-817. eCollection 2023.
Cancer stem cells (CSCs) are a subset of cancer cells with stem cell characteristics. The discovery of CSCs has opened a new era for cancer research. CSCs not only play a critical role in tumorigenesis, but also are responsible for the failure of cancer treatments. Here, we performed weighted gene co-expression network analysis (WGCNA) to identify key stemness genes and prognostic signatures using the data of an Asian liver cancer patient cohort and a White liver cancer patient cohort in The Cancer Genome Atlas (TCGA) database. To compare the difference in tumorigenesis between the Asian patients and the White patients, the prognostic value of the key genes from the Asian patients was evaluated in the White patient cohort and vice versa. We found that some key genes could predict the survival of the patients regardless of race. In addition, the key genes, NUCB2 and KLF4A, were selected from Asian patients and White patients, respectively, for further experimental validation. Knocking down NUCB2 could inhibit the activity of the AKT/mTOR signaling pathway and reverse the epithelial-mesenchymal transition (EMT) in liver cancer cells. We also confirmed that the knockdown of KLF4A suppressed ABCG2 activity and reduced the side population (SP) in liver cancer cells for the first time. Our results suggest that the stemness index is a useful method to identify key genes in tumorigenesis. Compared to the analysis for all patients, applying this index to the analysis of the patients of different races will provide more potential therapeutic targets for cancer treatment.
癌症干细胞（CSCs）是具有干细胞特征的癌细胞亚群。癌症干细胞的发现开启了癌症研究的新时代。癌症干细胞不仅在肿瘤发生中起关键作用，还导致癌症治疗失败。在此，我们进行了加权基因共表达网络分析（WGCNA），以使用癌症基因组图谱（TCGA）数据库中的亚洲肝癌患者队列和白人肝癌患者队列的数据来识别关键干性基因和预后特征。为了比较亚洲患者和白人患者在肿瘤发生方面的差异，在白人患者队列中评估了来自亚洲患者的关键基因的预后价值，反之亦然。我们发现一些关键基因可以预测患者的生存情况，而与种族无关。此外，分别从亚洲患者和白人患者中选择关键基因NUCB2和KLF4A进行进一步的实验验证。敲低NUCB2可抑制肝癌细胞中AKT/mTOR信号通路的活性并逆转上皮-间质转化（EMT）。我们还首次证实敲低KLF4A可抑制肝癌细胞中ABCG2的活性并减少侧群细胞（SP）。我们的结果表明，干性指数是识别肿瘤发生中关键基因的有用方法。与对所有患者的分析相比，将该指数应用于不同种族患者的分析将为癌症治疗提供更多潜在的治疗靶点。
