The AMPK-related kinase NUAK2 is speculated to play a major role in melanoma development and progression. In our past studies, we showed that NUAK2 is a gene that has a prognostic significance in acral melanoma patients by verifying a public array comparative genomic hybridization (CGH) database and immunohistochemistry of 56 primary acral melanomas (PNAS, 2011) and that pharma cologic inhibition of CDK2 is sufficient to suppress the growth of NUAK2 amplified and PTEN-deficient melanoma cells (Cancer Res, 2015). This time, in order to validate the previous survival data with an increased number of cases, we performed immunohistochemical analyses using 133 specimens of acral melanomas. We also examined its relevance with DNA copy number gains revealed by metaphase CGH. We performed immunohistochemical analyses by using formalin-fixed, paraffin-embedded tissues from 133 acral melanomas and 85 Non-CSD melanomas, and performed metaphase CGH analyses from 12 acral melanomas and 6 Non-CSD melanomas. The Kaplan-Meier curves showed that both the relapse-free survival and the overall survival time of patients with acral melanomas expressing NUAK2 were significantly shorter than patients without the NUAK2 expression. The Cox regression model showed a significant difference in relapse-free survival in acral melanomas. All 6 cases with 1q32 gain, where NUAK2 resides, over-express NUAK2. These data demonstrate that over-expression of NUAK2 has a significant influence on the survival of acral melanoma patients. We revalidated the previous data with an increased number of cases with acral melanomas.

NUAK2 over expressed and DNA copy number increased in acral melanoma: its significance on the survival of patients