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

Publication date: Available online 13 February 2018
Source:Human Pathology
Author(s): Tianxiao Xu, Meng Ma, Jie Dai, Sifan Yu, Xiaowen Wu, Huan Tang, Jiayi Yu, Junya Yan, Huan Yu, Zhihong Chi, Lu Si, Xinan Sheng, Chuanliang Cui, Yan Kong, Jun Guo
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 six 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 (si)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 TNM (tumor-node-metastases) stages (P=.025) and a shorter disease-free survival (DFS) in patients with AM (P=.038). Cox regression assays showed that high CDCA5 expression was also an independent factor of DFS for patients with AM (hazard ratio [HR] =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.



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