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GDF11 upregulation independently predicts shorter overall-survival of uveal melanoma.
PLOS ONE ( IF 2.9 ) Pub Date : 2019-03-18 , DOI: 10.1371/journal.pone.0214073 Xun Liu 1 , Qinghai Zhang 2 , Chuanfeng Fan 3 , Jie Tian 1 , Xinchang Liu 1 , Guofeng Li 1
PLOS ONE ( IF 2.9 ) Pub Date : 2019-03-18 , DOI: 10.1371/journal.pone.0214073 Xun Liu 1 , Qinghai Zhang 2 , Chuanfeng Fan 3 , Jie Tian 1 , Xinchang Liu 1 , Guofeng Li 1
Affiliation
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Growth differentiation factor 11 (GDF11), is a member of the transforming growth factor-beta (TGF-β) superfamily and bone morphogenetic protein (BMP) subfamily. In this study, we aimed to assess the expression profile of GDF11, its prognostic value in terms of OS, as well as the potential mechanisms leading to its dysregulation in uveal melanoma. A retrospective study was conducted using our primary data and genetic, clinicopathological and overall survival (OS) data from the Cancer Genome Atlas-Uveal Melanoma (TCGA-UVM). Results showed that GDF11 expression was significantly higher in tumor tissues compared with that in adjacent normal tissues. High GDF11 expression was associated with uveal melanoma in advanced stages (IV), epithelioid cell dominant subtype, as well as extrascleral extension. Univariate analysis showed that older age, epithelioid cell dominant, with extrascleral extension and increased GDF11 expression were associated with unfavorable OS. Multivariate analysis confirmed that GDF11 expression was an independent prognostic indicator of unfavorable OS (HR: 1.704, 95%CI: 1.143-2.540, p = 0.009), after adjustment of age, histological subtypes and extrascleral extension. Among the 80 cases of uveal melanoma, only 3 cases had low-level copy gain (+1) and 2 cases had heterozygous loss (-1). No somatic mutations, including SNPs and small INDELs were observed in GDF11 DNA. The methylation of these four CpG sites had weakly (cg22950598 and cg23689080), moderately (cg09890930), or strongly (cg05511733) negative correlation with GDF11 expression. In addition, the patients with high methylation of these four sites had significantly better OS compared to the group with low methylation. Based on these findings, we infer that methylation modulated GDF11 expression might be a valuable prognostic biomarker regarding OS in uveal melanoma.
中文翻译：
GDF11上调独立预测葡萄膜黑色素瘤的总体生存期较短。
生长分化因子11（GDF11）是转化生长因子β（TGF-β）超家族和骨形态发生蛋白（BMP）亚家族的成员。在这项研究中，我们旨在评估GDF11的表达谱，其在OS方面的预后价值以及导致其在葡萄膜黑色素瘤中失调的潜在机制。使用我们的主要数据以及癌症基因组图谱-葡萄膜黑色素瘤（TCGA-UVM）的遗传，临床病理和整体生存（OS）数据进行了回顾性研究。结果显示，与邻近的正常组织相比，GDF11在肿瘤组织中的表达明显更高。GDF11高表达与晚期葡萄膜黑色素瘤（IV），上皮样细胞显性亚型以及巩膜外延伸有关。单因素分析显示，年龄较大，上皮样细胞显性，巩膜外延伸和GDF11表达增加与OS不良有关。多变量分析证实，在调整年龄，组织学亚型和巩膜外延伸后，GDF11表达是OS不良的独立预后指标（HR：1.704，95％CI：1.143-2.540，p = 0.009）。在葡萄膜黑色素瘤的80例病例中，只有3例具有低水平的复制增加（+1）和2例具有杂合性缺失（-1）。在GDF11 DNA中未观察到体细胞突变，包括SNP和小的INDEL。这四个CpG位点的甲基化与GDF11表达呈弱负相关（cg22950598和cg23689080），中度（cg09890930）或强（cg05511733）负相关。此外，与甲基化程度低的组相比，这四个部位的甲基化程度高的患者的OS明显更好。基于这些发现，我们推断甲基化调节的GDF11表达可能是关于葡萄膜黑色素瘤OS的有价值的预后生物标志物。
更新日期：2019-03-19
中文翻译：
GDF11上调独立预测葡萄膜黑色素瘤的总体生存期较短。
生长分化因子11（GDF11）是转化生长因子β（TGF-β）超家族和骨形态发生蛋白（BMP）亚家族的成员。在这项研究中，我们旨在评估GDF11的表达谱，其在OS方面的预后价值以及导致其在葡萄膜黑色素瘤中失调的潜在机制。使用我们的主要数据以及癌症基因组图谱-葡萄膜黑色素瘤（TCGA-UVM）的遗传，临床病理和整体生存（OS）数据进行了回顾性研究。结果显示，与邻近的正常组织相比，GDF11在肿瘤组织中的表达明显更高。GDF11高表达与晚期葡萄膜黑色素瘤（IV），上皮样细胞显性亚型以及巩膜外延伸有关。单因素分析显示，年龄较大，上皮样细胞显性，巩膜外延伸和GDF11表达增加与OS不良有关。多变量分析证实，在调整年龄，组织学亚型和巩膜外延伸后，GDF11表达是OS不良的独立预后指标（HR：1.704，95％CI：1.143-2.540，p = 0.009）。在葡萄膜黑色素瘤的80例病例中，只有3例具有低水平的复制增加（+1）和2例具有杂合性缺失（-1）。在GDF11 DNA中未观察到体细胞突变，包括SNP和小的INDEL。这四个CpG位点的甲基化与GDF11表达呈弱负相关（cg22950598和cg23689080），中度（cg09890930）或强（cg05511733）负相关。此外，与甲基化程度低的组相比，这四个部位的甲基化程度高的患者的OS明显更好。基于这些发现，我们推断甲基化调节的GDF11表达可能是关于葡萄膜黑色素瘤OS的有价值的预后生物标志物。
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