Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma

• Published in: Laboratory investigation Vol. 98; no. 3; pp. 327 - 338
• Main Authors: Leonard, M Kathryn, McCorkle, Joseph R, Snyder, Devin E, Novak, Marian, Zhang, Qingbei, Shetty, Amol C, Mahurkar, Anup A, Kaetzel, David M
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.03.2018; Nature Publishing Group US; Nature Publishing Group
• Subjects: 692/420/755; 692/699/67/1813; Animals; Antigens, Neoplasm - genetics; Bioinformatics; Cancer; Cell Line, Tumor; Chemokine CXCL11 - genetics; Computational Biology; CXCL11 protein; Female; Fructose-Bisphosphate Aldolase - genetics; Gene expression; Gene Expression Regulation, Neoplastic; Genes; Genomes; Humans; Laboratory Medicine; Medicine; Medicine & Public Health; Melanoma; Melanoma - metabolism; Melanoma - mortality; Metastases; Metastasis; Mice, Nude; Molecular modelling; Neoplasm Metastasis; NM23 Nucleoside Diphosphate Kinases - genetics; NM23 Nucleoside Diphosphate Kinases - metabolism; Pathology; Patients; Point Mutation; Receptors, LDL - genetics; research-article; Survival; Therapeutic applications
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.2017.108

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.