Volume 29, Issue 4, 2020

DOI: 10.24205/03276716.2020.838

Integrated Analysis of a Gene Signature for Prognosis Prediction in Uveal Melanoma

Background: Uveal melanoma (UVM) is a rare disease but most common primary intraocular malignant tumor among adults. The destructive degree of this tumor is high with poor prognosis. Therefore, it is urgent to discover novel prognosis biomarkers of uveal melanoma. Methods: mRNA expression patterns were examined in 80 UVM samples collected from the Cancer Genome Atlas. Univariate Cox regression and Lasso regression analysis were used to evaluate the associations between genes and survival time. A risk score based on genes was calculated to assess the predictive value. ROC (Receiver Operating Characteristics) analysis was applied to assess the sensitivity of survival prediction. Pseudogene–miRNA–mRNA network was visualized by Cytoscape. Results: With univariate Cox regression and Lasso regression analyses, the expression level of six genes (CLNS1AP1, MAST4-AS1, MIR6870, NIPA2P1, PADI3, and SPRR4) was significantly correlated with survival time of UVM patients. Based on risk score, patients were divided into a high-risk and low-risk group. Interestingly, the identified genes were nearly just associated with the survival risk in UVM. Moreover, we predicted miRNAs (hsa-miR-580-3p, hsa-miR-520a-5p, and hsa-miR-525-5p) that bound to the pseudogene CLNS1AP1. BCL2L1, FOXO3, FOXL2, TWIST1, PARP1 and VDR were identified as the potential targets of CLNS1AP1. Conclusions: CLNS1AP1, MAST4-AS1, MIR6870, NIPA2P1, PADI3, and SPRR4 were identified as potential biomarkers of UVM. We constructed the pseudogene–miRNA–mRNA network of CLNS1AP1 and discussed its potential mechanism. This work may have important implications in the understanding of the potential prognostic value of gene-based signatures in UVM.

uveal melanoma; risk score; CLNS1AP1; pseudogene–miRNA–mRNA

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