Gene expression screening identifies CDCA5 as a potential therapeutic target in acral melanoma

Acral melanoma (AM) is a rapidly progressing subtype of melanoma with poor prognosis. The complete array of molecular changes that occur during AM metastasis remains unclear. In this study, we compared the gene expression profiles of 6 primary and 12 lymph node metastatic AM samples by tissue microarray analysis. We found that the expression levels of 396 genes were increased and that of 766 genes were decreased in the metastatic tissues compared with that in the primary tumors. The top 19 genes upregulated in the metastatic tissue specimens were selected for high-content short interfering RNA screening. We found that inhibition of cell division cycle-associated 5 (CDCA5) significantly suppressed AM cell migration and invasion. Furthermore, we demonstrated that upregulation of CDCA5 was correlated with higher tumor-node-metastases stages (P=.025) and a shorter disease-free survival in patients with AM (P=.038). Cox regression analyses showed that high CDCA5 expression was also an independent factor of disease-free survival for patients with AM (hazard ratio =1.86, P=.041). Overall, our data define the gene expression signature of AM metastasis and indicate that CDCA5 is a potential therapeutic target in AM.