Abstract：
Uveal melanoma (UM) is a deadly ocular malignancy, originating from uveal melanocytes. Although much is known regarding prognostication in UM, the exact mechanism of metastasis is mostly unknown. Metastatic tumor cells are known to express a more stem-like RNA profile which is seen often in cell-specific embryonic development to induce tumor progression. Here, we identified novel transcription regulators by reanalyzing publicly available single cell RNA sequencing experiments. We identified five transcription regulators of interest: ELL2, KDM5B, REXO4, RBFOX2 and FOXD1. Our most significant finding is FOXD1, as this gene is nearly exclusively expressed in high-risk UM and its expression is associated with a poor prognosis. Even within the BAP1-mutated UM, the expression of FOXD1 is correlated with poor survival. FOXD1 is a novel factor which could potentially be involved in the metastatic capacity of high-risk UM. Elucidating the function of FOXD1 in UM could provide insight into the malignant transformation of uveal melanocytes, especially in high-risk UM.
摘要：
葡萄膜黑色素瘤（UM）是一种致命的眼部恶性肿瘤，来源于葡萄膜黑素细胞.尽管人们对UM中的预测了解很多，转移的确切机制尚不清楚。已知转移性肿瘤细胞表达更多的干细胞样RNA谱,这在细胞特异性胚胎发育中经常看到以诱导肿瘤进展。这里,我们通过重新分析公开的单细胞RNA测序实验发现了新的转录调节因子.我们确定了五个感兴趣的转录调节因子：ELL2，KDM5B，REXO4、RBFOX2和FOXD1。我们最重要的发现是FOXD1，因为该基因几乎仅在高危UM中表达，并且其表达与不良预后有关。即使在BAP1突变的UM中，FOXD1的表达与低生存率相关。FOXD1是一种新的因子，可能与高危UM的转移能力有关。阐明FOXD1在UM中的功能可以深入了解葡萄膜黑素细胞的恶性转化，尤其是高危人群。
