Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma.
Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma.
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DOI：
10.1038/labinvest.2017.108
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Kaetzel DM
中科院分区：
文献类型：
--
作者：
Leonard MK;McCorkle JR;Snyder DE;Novak M;Zhang Q;Shetty AC;Mahurkar AA;Kaetzel DM
虽然NME 1因其抑制黑素瘤转移的能力而众所周知，但这种活性的分子机制尚未完全理解。在此，我们利用生物信息学方法系统地鉴定了其表达与NME 1转移抑制功能相关的基因。这是通过搜索受NME 1调节的基因，但不是由缺乏转移抑制活性的NME 1变体来实现的。该方法鉴定了许多新基因，如ALDOC、CXCL11、LRP 1b和XAGE 1以及已知靶点如NETO 2，它们被统称为NME 1调节的转移抑制因子标签（MSS）。癌症基因组图谱（TCGA）中的一个大型黑色素瘤患者队列中，MSS与总生存期延长相关。MSS基因表达升高的黑色素瘤患者的中位总生存期比MSS基因表达较低的患者长5.6年以上。这些数据表明，NME1代表了用于鉴定其表达与黑素瘤患者的转移和存活相关的基因的有力工具，表明其作为该致死性癌症的晚期形式中的预后标志物和治疗靶标的潜在应用。
While 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 greater than 5.6 years longer than 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.
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影响因子：
11.2
作者：
Jarrett SG;Novak M;Dabernat S;Daniel JY;Mellon I;Zhang Q;Harris N;Ciesielski MJ;Fenstermaker RA;Kovacic D;Slominski A;Kaetzel DM
通讯作者：
Kaetzel DM
影响因子：
8
作者：
通讯作者：
--
影响因子：
3.7
作者：
Cunha, Elizabeth S.;Kawahara, Rebeca;Martinez, Glaucia R.
通讯作者：
Martinez, Glaucia R.
影响因子：
6
作者：
Calicchio, Monica L.;Collins, Tucker;Kozakewich, Harry P.
通讯作者：
Kozakewich, Harry P.
影响因子：
2.1
作者：
Irizarry, RA;Hobbs, B;Speed, TP
通讯作者：
Speed, TP