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

Rotterdam Ocular Melanoma Study Group, Quincy C C van den Bosch, Josephine Q N Nguyen, 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

5 Citations (Scopus)
38 Downloads (Pure)

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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