Eye Pathology Institute, University of Copenhagen, Copenhagen, Denmark.
Acta Ophthalmol. 2014 Sep;92(6):541-9. doi: 10.1111/aos.12322. Epub 2013 Dec 24.
To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM).
Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation-dependent probe amplification (MLPA) was used to identify chromosomal changes. Chromosomal changes and clinicopathological data were correlated with survival and metastasis. The microRNA expression was analysed in 26 of the 36 archived UM samples. Unsupervised analysis, differential expression analysis and Cox regression analysis were performed to determine the association with metastasis and survival.
Metastasis and metastatic death occurred in 20 patients, two patients died of other causes and one patient of unknown causes. A significant association between increasing size category (p = 0.002, log-rank), extraocular extension (p = 0.001), chromosome 3 loss (p = 0.033) and 1p loss (p = 0.030) and development of metastases was observed. Tumour, node, metastasis (TNM) staging showed a significant association with survival (p < 0.0001, log-rank). Adjusting for gender and age TNM size category T4 (p = 0.016, Cox regression analysis), mixed (p = 0.029) and epithelioid (p = 0.0058) cell types, chromosome 3 loss (p = 0.014) and 8q gain (p = 0.010) were significant prognosticators for a poor survival. Hierarchical clustering divided the UM into three groups based on microRNA expression. The clusters showed no association with clinical or histopathological features, TNM staging, metastasis or survival. Differential expression analysis did not reveal microRNAs related to metastasis or survival.
The prognostic significance of chromosome 3 loss and 8q gain identified by MLPA analysis was confirmed in archived UM samples. The value of microRNA expression as a predictor of metastasis and survival in UM could not be confirmed.
确定微小 RNA 表达和染色体改变与葡萄膜黑色素瘤（UM）转移和生存的关系。
根据转移状态选择了 36 名 UM 患者，并收集了临床病理数据。采用多重连接依赖性探针扩增（MLPA）来识别染色体改变。将染色体改变和临床病理数据与生存和转移相关联。对 36 个存档的 UM 样本中的 26 个进行了 microRNA 表达分析。进行无监督分析、差异表达分析和 Cox 回归分析，以确定与转移和生存的关系。
20 名患者发生转移和转移性死亡，2 名患者死于其他原因，1 名患者死因不明。肿瘤大小类别增加（p=0.002，对数秩检验）、眼外扩展（p=0.001）、3 号染色体缺失（p=0.033）和 1p 缺失（p=0.030）与转移的发展显著相关。肿瘤、淋巴结、转移（TNM）分期与生存显著相关（p<0.0001，对数秩检验）。调整性别和年龄后，TNM 大小类别 T4（p=0.016，Cox 回归分析）、混合（p=0.029）和上皮样（p=0.0058）细胞类型、3 号染色体缺失（p=0.014）和 8q 增益（p=0.010）是生存不良的显著预后因素。基于 microRNA 表达的层次聚类将 UM 分为三组。聚类与临床或组织病理学特征、TNM 分期、转移或生存均无关联。差异表达分析未发现与转移或生存相关的 microRNAs。
MLPA 分析确定的 3 号染色体缺失和 8q 增益的预后意义在存档的 UM 样本中得到了证实。microRNA 表达作为 UM 转移和生存预测因子的价值尚未得到证实。
