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.
Highlights
Uveal melanoma (UM) is the most common primary intraocular cancer occurring in adults [1, 2]
The development of metastases plays an important role in UM patient prognosis
Molecular biomarkers associated with UM metastasis may help in accurately identifying high-risk patients and in discovering potential therapeutic targets for metastatic UM treatment
Summary
Uveal melanoma (UM) is the most common primary intraocular cancer occurring in adults [1, 2]. For patients with metastatic UM, the 1-year survival rate is 20%, the 5-year survival rate is less than 5%, and the median overall survival is only 6–12 months [1, 5,6,7,8]. There is no effective therapeutic intervention to treat metastatic UM [4]. While UM may bear histologic resemblance to its more-common cutaneous counterpart, it is considered molecularly distinct. In contrast to cutaneous melanoma, UM has a lower mutational burden [9] and lacks characteristic BRAF and NRAS mutations [9, 10]. Most UM tumors contain GNAQ or GNA11 mutations [11], MAPK pathway activations [12], and cytogenetic abnormalities (monosomy 3 and trisomy 8q) [13]
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