Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland-Baltimore, Baltimore, MD, USA.
Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland-Baltimore, Baltimore, MD, USA.
Lab Invest. 2018 Mar;98(3):327-338. doi: 10.1038/labinvest.2017.108. Epub 2017 Oct 23.
Although NME1 is well known for its ability to suppress metastasis of melanoma, the molecular mechanisms underlying this activity are not completely understood. Herein, we utilized a bioinformatics approach to systematically identify genes whose expression is correlated with the metastasis suppressor function of NME1. This was accomplished through a search for genes that were regulated by NME1, but not by NME1 variants lacking metastasis suppressor activity. This approach identified a number of novel genes, such as ALDOC, CXCL11, LRP1b, and XAGE1 as well as known targets such as NETO2, which were collectively designated as an NME1-Regulated Metastasis Suppressor Signature (MSS). The MSS was associated with prolonged overall survival in a large cohort of melanoma patients in The Cancer Genome Atlas (TCGA). The median overall survival of melanoma patients with elevated expression of the MSS genes was >5.6 years longer compared with that of patients with lower expression of the MSS genes. These data demonstrate that NMEl represents a powerful tool for identifying genes whose expression is associated with metastasis and survival of melanoma patients, suggesting their potential applications as prognostic markers and therapeutic targets in advanced forms of this lethal cancer.
尽管 NME1 以其抑制黑色素瘤转移的能力而闻名，但这一活性背后的分子机制尚不完全清楚。在此，我们利用生物信息学方法系统地鉴定了与 NME1 转移抑制功能相关的表达基因。这是通过寻找受 NME1 调节但不受缺乏转移抑制活性的 NME1 变体调节的基因来实现的。这种方法鉴定了许多新的基因，如 ALDOC、CXCL11、LRP1b 和 XAGE1 以及 NETO2 等已知靶点，这些基因被统称为 NME1 调节的转移抑制标志（MSS）。在癌症基因组图谱（TCGA）中一个大型黑色素瘤患者队列中，MSS 与延长的总体生存率相关。与 MSS 基因表达较低的患者相比，MSS 基因表达升高的黑色素瘤患者的中位总体生存率延长了超过 5.6 年。这些数据表明，NME1 是一种强大的工具，可用于鉴定与黑色素瘤患者转移和生存相关的表达基因，表明它们作为该致命癌症晚期的预后标志物和治疗靶点具有潜在的应用价值。
