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

TL;DR

This study identifies gene patterns in feline eye tumors that could help predict disease severity and guide future treatments.

Contribution

The study provides novel transcriptomic biomarkers for predicting the severity of feline diffuse iris melanoma.

Findings

Early FDIM shows upregulated genes linked to tumor initiation and immune recruitment.

Late FDIM is characterized by immune evasion and apoptosis inhibition gene expression.

Iris melanosis overlaps genetically with early FDIM, suggesting it is an early stage of melanoma.

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-naïve 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.

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