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

Abstract

SummaryWhile 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.

Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis

“…Still, increased levels of NME1 negatively correlated with disease stage while NME1 upregulation was positively correlated with poor overall survival and with higher recurrence [55]. Furthermore, in melanoma patients, a NME1-related gene expression signature was reported and linked with increased overall survival [57], pinpointing for a potential tumor suppressor role, but new pro-oncogenic roles, mainly related with the expansion of stem-like features and tumor growth, were recently reported [58]. Considering CDS1, a DNA damage-related function is well-known [59,60] and a screening of several cancer cell lines highlighted that the expression levels of CDS1 are dependent on p53 activity, being inversely correlated with the presence of a functional p53 [61].…”

Biomarkers Associated with Tumor Heterogeneity in Prostate Cancer

“…These genes were PTEN , CDC42EP5 , RNLS, GP2 , NETO2 , and AMPD3 . Overexpression of Neuropilin and tolloid-like 2 ( NETO2 ) has been found in many cancer types including proliferating hemangiomas and colorectal carcinoma [24] , [25] , [26] and thus could be considered as a potential biomarker in tumor progression. Recent study have suggested that adenosine monophosphate deaminase 3 ( AMPD3 ) deletion suppresses the proliferation, migration, and invasion of gastrointestinal stromal tumor [27] .…”

NME/NM23/NDPK and Histidine Phosphorylation

“…Interestingly, NME1 directly enhances the expression of aldolase C by binding to its promoter [91]. Moreover, using a bioinformatics approach, aldolase C has been identified as one of the genes establishing the NME1-regulated Metastasis Suppressor Signature (MSS) [92]. It would be of interest to see if other genes that make up the MSS are also phosphorylated by NME on histidine or aspartate.…”