FOXD1 Is a Transcription Factor Important for Uveal Melanocyte Development and Associated with High-Risk Uveal Melanoma

Quincy C.C. van den Bosch, Josephine Q.N. Nguyen, on behalf of the Rotterdam Ocular Melanoma Study Group, Tom Brands, Thierry P.P. van den Bosch, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, Emine Kiliç*, Erwin Brosens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number3668
JournalCancers
Volume14
Issue number15
DOIs
Publication statusPublished - Aug 2022

Bibliographical note

Funding Information:
This research was funded by the Henkes foundation (2021-04) J.Q.N.N., E.K.; Rotterdamse Blindenbelangen (HV/AB/B20200043) Q.C.C.v.d.B., E.B.; Collaborative Ophthalmic Research Rotterdam (6.2.0) J.Q.N.N., E.K.; Landelijke Stichting voor Blinden en Slechtzienden (2019-7) Q.C.C.v.d.B., E.B.; and Algemene Nederlandse Vereniging ter voorkoming van Blindheid (2019-07) Q.C.C.v.d.B., E.B.

Publisher Copyright:
© 2022 by the authors.

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