TY - JOUR
T1 - FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma
AU - van den Bosch, Quincy C C
AU - Nguyen, Josephine Q N
AU - Brands, Tom
AU - van den Bosch, Thierry P P
AU - Verdijk, Robert M
AU - Paridaens, Dion
AU - Naus, Nicole C
AU - de Klein, Annelies
AU - Kiliç, Emine
AU - Brosens, Erwin
AU - Rotterdam Ocular Melanoma Study Group
PY - 2022/7/28
Y1 - 2022/7/28
N2 - 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.
AB - 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.
KW - in silico analysis
KW - melanocyte development
KW - transcription factor
UR - https://www.mendeley.com/catalogue/f47eb3c1-3ee4-33aa-a94c-19c5c3fc744b/
U2 - 10.3390/cancers14153668
DO - 10.3390/cancers14153668
M3 - Article
C2 - 35954332
SN - 2072-6694
VL - 14
SP - 3668
JO - Cancers
JF - Cancers
IS - 15
ER -