Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou 333, Taiwan.
Int J Mol Sci. 2020 Apr 20;21(8):2881. doi: 10.3390/ijms21082881.
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, 's role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to . The results suggest that is epigenetically repressed in tumor tissue and that lower is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by . Furthermore, and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low . Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3X/SPINK1/metallothionein axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low expression levels.
X 连锁 DEAD（Asp-Glu-Ala-Asp）框多肽 3（DDX3X）是 DEAD 框家族 RNA 解旋酶的成员，其功能已被揭示涉及 RNA 代谢。最近的研究进一步表明，其在多种癌症中的异常表达及其对调节癌症进展的相关生物学效应。然而，其在肾细胞癌（RCC）进展中的作用在很大程度上仍然未知。在本研究中，使用癌症基因组图谱（TCGA）数据集进行了基于医学信息学的分析，以评估与 相关的临床预后。结果表明， 在肿瘤组织中存在表观遗传抑制，并且较低的 与 RCC 患者的整体生存率差、肿瘤大小大、淋巴结转移和远处转移（TNM 分期系统）相关。此外，通过 IPA 进行的基于知识的转录组分析显示，SPINK1-金属硫蛋白途径是受 抑制的顶级 1 个经典信号通路。此外， 和金属硫蛋白基因家族均作为不良预后指标，这些基因的表达水平与 RCC 中的 呈负相关。此外，通过连接性映射分析（L1000）鉴定出地高辛能够逆转低 的患者的基因特征。重要的是，地高辛处理可降低 RCC 细胞中的癌细胞增殖和迁移。本研究的结果表明，DDX3X/SPINK1/金属硫蛋白轴对预测 RCC 患者生存不良结局具有重要意义，并表明地高辛是治疗低 表达水平患者的精确和个性化化合物。
