Uncovering the molecular signature of feline diffuse iris melanoma through transcriptomic analysis of disease severity

Kayes, D; Blacklock, B; McGeachan, R; Scurrell, E; Donnelly, K; Murphy, L; Fawkes, A; Clark, R; Meynert, A; Becher, H; Pittaway, R; Fricker, G; Pont, RT; Suárez-Bonnet, A; Blacklock, KLB

Abstract

Feline diffuse iris melanoma (FDIM) is the most common primary ocular tumour in cats, with metastatic disease occurring in 19-63% of patients. Greater intraocular invasion correlates with increased mortality. No effective therapeutics exist for metastatic FDIM, partly due to a lack of known molecular targets associated with aggressive tumour behaviour. Here, we define the transcriptomic landscape of FDIM in treatment-na & iuml;ve cats using bulk RNA sequencing on laser capture microdissection and core biopsy specimens from formalin-fixed paraffin-embedded tissue. Samples included 'iris melanosis' (dysplastic melanocytes confined to the anterior iris; n = 7), 'early FDIM' (neoplastic melanocytes confined to the iris stroma; n = 13), and 'late FDIM' (neoplastic infiltration into the ciliary body and sclera; n = 13). Iris melanosis exhibited genetic overlap with early FDIM, supporting its reclassification as 'melanoma in situ'. Early FDIM showed upregulation of genes linked to tumour initiation, immune recruitment, and motility (e.g., STOX1, PEG3, XIAP, MCAM, VIM). Late FDIM exhibited immune microenvironment remodelling, immune evasion, and apoptosis inhibition (e.g., BIRC2, BIRC5, CCL2, HAVCR2), with downregulation of FOX1, FOXC2, and SOX11. These results provide critical biomarkers of disease severity, which may aid in the development of more accurate prognostic tests and more effective targeted therapies for FDIM.

Citation

Kayes, D., Blacklock, B., McGeachan, R., Scurrell, E., Donnelly, K., Murphy, L., Fawkes, A., Clark, R., Meynert, A., Becher, H., Pittaway, R., Fricker, G., Pont, R., Suárez-Bonnet, A., & Blacklock, K. (2025). Uncovering the molecular signature of feline diffuse iris melanoma through transcriptomic analysis of disease severity. Scientific Reports, 15(1), https://doi.org/10.1038/s41598-025-09632-5

• Journal Article Type: Article
• Acceptance Date: Jun 30, 2025
• Online Publication Date: Jul 19, 2025
• Publication Date: 2025
• Deposit Date: Jul 29, 2025
• Publicly Available Date: Jul 29, 2025
• Print ISSN: 2045-2322
• Electronic ISSN: 2045-2322
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 1
• DOI: https://doi.org/10.1038/s41598-025-09632-5
• Keywords: Feline diffuse iris melanoma; Melanoma metastasis; Transcriptome; Gene expression; Uveal melanoma; UVEAL MELANOMA; METASTATIC-DISEASE; GENE-EXPRESSION; FOXC1; PROGNOSIS; FEATURES; TRIALS