Dong Xueyi, Hong Yuheng, Sun Huizhi, Chen Chen, Zhao Xiulan, Sun Baocun
Department of Pathology, Tianjin Medical University, Tianjin 300070, P.R. China.
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin 300052, P.R. China.
Oncol Lett. 2019 Sep;18(3):3003-3016. doi: 10.3892/ol.2019.10642. Epub 2019 Jul 22.
N-myc downstream regulated gene 1 (NDRG1) has been well characterized as a suppressor of metastasis in numerous types of carcinoma. NDRG1 inhibits the metastatic progression of cancer cells via its inhibitory effects on a wide variety of cellular signaling pathways. Vasculogenic mimicry (VM) refers to the unique ability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks, and is the main reason for the poor prognosis and failure of antivascular therapy in gastric carcinoma (GC). Tumor cells can mimic the function of endothelial cells to exhibit VM through epithelial-mesenchymal transition (EMT). However, the potential function of NDRG1 in metastatic GC progression in patients has not yet been fully elucidated. To date, data regarding the function of NDRG1 in VM formation in GC have not been reported. The aim of the present study was to elucidate these unknown areas. To this end, 228 samples of human GC were used to identify the protein expression levels of NDRG1, VM-associated proteins and EMT-associated proteins via immunohistochemistry, and their clinical significance was assessed. In addition, the data of 415 patients with GC were collected from The Cancer Genome Atlas database. A functional enrichment analysis concerning NDRG1 was performed using Metascape and the Gene Set Enrichment Analysis (GSEA). In conclusion, the results of the present study indicate that NDRG1 is negatively correlated with poor prognosis through suppression of VM formation in GC. The results of the present study demonstrated that NDRG1 decreases EMT-associated protein expression and that HER2 expression may serve a significant role in this process. The Metascape and GSEA results also indirectly support this conclusion. The present study discusses the status NDRG1 as a prognostic and selective biomarker in GC, as well as current and future NDRG1-targeted therapies.
N-myc下游调控基因1（NDRG1）已被充分确认为多种类型癌症转移的抑制因子。NDRG1通过对多种细胞信号通路的抑制作用，抑制癌细胞的转移进程。血管生成拟态（VM）是指侵袭性肿瘤细胞模拟胚胎血管生成网络模式的独特能力，是胃癌（GC）预后不良和抗血管生成治疗失败的主要原因。肿瘤细胞可通过上皮-间质转化（EMT）模拟内皮细胞功能以展现VM。然而，NDRG1在GC患者转移进展中的潜在功能尚未完全阐明。迄今为止，关于NDRG1在GC中VM形成的功能的数据尚未见报道。本研究的目的是阐明这些未知领域。为此，使用228例人GC样本通过免疫组织化学鉴定NDRG1、VM相关蛋白和EMT相关蛋白的蛋白表达水平，并评估其临床意义。此外，从癌症基因组图谱数据库收集了415例GC患者的数据。使用Metascape和基因集富集分析（GSEA）对NDRG1进行功能富集分析。总之，本研究结果表明，NDRG1通过抑制GC中的VM形成与不良预后呈负相关。本研究结果表明，NDRG1降低EMT相关蛋白表达，且HER2表达可能在此过程中起重要作用。Metascape和GSEA结果也间接支持这一结论。本研究讨论了NDRG1作为GC预后和选择性生物标志物的地位，以及当前和未来针对NDRG1的治疗方法。
