Abstract
BACKGROUND: An increasing amount of research over recent years on the anti-metastasis function of the non-metastatic (NME) gene family has been challenged, with some studies identifying its involvement in the promotion of oncogenesis. Therefore, the specific functions of the NME gene family require redefining through a comprehensive analysis of tumor heterogeneity and survival benefit. However, the functions of NME genes have not been comprehensively investigated in breast cancer (BC). METHODS: In this study, ONCOMINE, GEPIA, Kaplan-Meier plotter, cBioPortal, String, and metascape databases were utilized for comparison of the mRNA expression, patient survival and network analysis of NME-associated signaling pathways in BC patients. RESULTS: The mRNA expression of NME1 and NME2 was significantly increased in BC. Additionally, high NME 1 and NME2 levels were related to poor overall survival (OS), while the upregulated expression of NME3, NME5, and NME7 indicated prolonged survival. Moreover, increased mRNA level, amplification, or deep deletions in the NME gene family were identified in approximately 41% (450/1098) of all included BC specimens. NME1 and NME2 genes displayed the highest correlation with genetic correlations of the human NME genes in BC. The following pathways were regulated by NME gene upregulation: R-HAS-380270: Recruitment of mitotic centrosome and complexes; GO:0006228: UTP biosynthetic process; R-HAS-380259: Loss of NlP from mitotic centrosomes; hsa03410: Base excision repair; and CORUM:3714: Pericenrin-GCP complex, which was significantly modulated by changes influencing the NME genes. CONCLUSIONS: Collectively, our findings revealed that the elevated expression of NME1 and NME2 could act as a biomarker and predictive tool for BC patients with poor prognosis. Furthermore, our findings indicated that NME3, NME5, and NME7 might play the roles of tumor suppressor genes, which require validation through further experiments.