High expression of lncRNA PVT1 independently predicts poor overall survival in patients with primary uveal melanoma.

Haiming Xu,Jingwen Gong,Hui Liu,Andrzej T Slominski

doi:10.1371/journal.pone.0189675

Haiming Xu, Jingwen Gong + Show 2 more

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https://doi.org/10.1371/journal.pone.0189675

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Abstract

The plasmacytoma variant translocation 1 gene (PVT1) plays an oncogenic role in the initiation and progression of multiple cancers. In this study, by using deep-sequencing data and follow-up data in the Cancer Genome Atlas-Uveal melanomas (TCGA-UVM), we assessed the association between the expression of PVT1 and clinicopathological characteristics of patients with uveal melanoma, the mechanism of its dysregulation and its prognostic value. Results showed that high PVT1 expression group had a higher proportion of epithelioid cell dominant disease (a more malignant histological subtype than spindle cell dominant disease) and more cases of extrascleral extension (a risk factor for metastasis) compared with the low PVT1 expression group. 61 out of 80 cases (76.3%) of primary uveal melanoma had PVT1 amplification in TCGA-UVM. In addition, PVT1 expression was strongly and negatively correlated with its methylation status (Pearson's r = -0.712, Spearman’s r = -0.806). By performing univariate and multivariate analysis, we found that high PVT1 expression was an independent predictor of poor OS in patients with uveal melanoma (HR: 12.015, 95%CI: 1.854–77.876, p = 0.009). Based on these findings, we infer that PVT1 expression is modulated by both DNA amplification and methylation and its expression might serve as a valuable and specific prognostic biomarker in terms of OS in uveal melanoma.

Highlights

Long noncoding RNAs are a class of RNA that are longer than 200 nucleotides and do not code for proteins [1]
High expression of Long noncoding RNAs (lncRNAs) plasmacytoma variant translocation 1 gene (PVT1) is associated with malignant behaviors of uveal melanoma
Compared with the low PVT1 expression group, the high PVT1 expression was associated with older age (66.80 ± 11.55 vs. 56.50 ± 14.36, p = 0.0007), a higher proportion of epithelioid cell dominant disease (22/40 vs. 12/40, p = 0.024), more cases of distant metastasis (4/28 vs. 0/27, p = 0.043) and extrascleral extension (6/37 vs. 1/38, p = 0.043) and a higher death rate (20/40 vs. 3/40, p

Summary

Introduction

Long noncoding RNAs (lncRNAs) are a class of RNA that are longer than 200 nucleotides and do not code for proteins [1]. Previous studies found that this class of RNAs play a pivotal role in regulating gene expression at both transcriptional and post-transcriptional levels [1]. Uveal melanoma, which is known as ocular melanoma is the most common primary intraocular cancer in adults. Some recent studies found that dysregulated lncRNAs are involved in the pathological development of uveal melanoma [2, 3]. Hypermethylated in cancer 1 (HIC1) can induce uveal melanoma progression by activating lncRNA-numb [4].

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