Changes in microRNA expression associated with metastasis and survival in patients with uveal melanoma

Abstract

Uveal melanoma (UM) is a major intraocular cancer that is molecularly distinct from cutaneous melanoma. Approximately half of patients with UM eventually develop metastasis. The prognosis of metastatic UM is poor, with a median overall survival (OS) of less than a year. In this study, we sought to identify microRNAs (miRNAs) associated with metastasis and OS in UM. We analyzed the miRNA expression and clinical outcomes data from The Cancer Genome Atlas (TCGA) dataset for UM. Differential expression analyses were conducted for each miRNA with respect ever-development of metastasis. Multiple survival analyses were done, using the Cox proportional hazards model, to evaluate interactions between miRNA expression, metastasis, and OS. A total of 22 miRNAs (3 upregulated and 19 downregulated) were differentially expressed between patients with vs. without metastatic UM. These 22 miRNAs could be grouped into four clusters based on similarities in expression patterns. Of the 22 miRNAs differentially expressed with respect to metastasis, 21 were significantly associated with OS. The expression of multiple miRNAs was significantly associated with metastasis and overall survival in patients with UM. Further investigation of these miRNAs as biomarkers and/or therapeutic targets is warranted in the push to improve outcomes for patients with metastatic UM.