Fig. 2

Transcriptomic analysis of feline diffuse iris melanoma (FDIM). The principal component analysis (PCA) plot grouping samples by the top 500 transcripts after variance-stabilising transformation of transcript counts (A). There is clear and separate clustering of the iris melanosis and late FDIM samples, with the early FDIM samples overlapping both groups, showing that early FDIM is an intermediate disease stage. Volcano plots highlight the number of significantly dysregulated transcripts between early FDIM and iris melanosis (Bi), late FDIM and iris melanosis (Ci) and between late and early FDIM (Di). A logfold-change threshold was set at − 1.5 and 1.5 and an adjusted P-value threshold of 0.05 was used. Ingenuity pathway analysis identified cancer and organismal injury and abnormalities to be the top dysregulated disease pathways between early FDIM and iris melanosis (Bii), late and iris melanosis (Cii) and late and early FDIM (Dii). The disease progression of FDIM is associated with key molecular events (E). Tumour initiation is associated with upregulation of STOX1, PEG3, XIAP and VIM, increasing invasive tendencies and immune cell recruitment. Progression to late FDIM is characterised by downregulation of SOX11, FOXC1 and FOXC2, likely leading to a more dedifferentiated and plastic cellular phenotype. Significant upregulation of BIRC2 and BIRC5 leads to inhibition of apoptosis. Additionally, upregulation of BIRC5, CCL2 and HAVCR2 lead to immune-microenvironment remodelling, associated with the M2 (immunosuppressive) tumour associated macrophages as well as T-regulator (Treg) cells and inhibition of cytotoxic T-cells (CTC), aiding immune escape. Created in BioRender. Kayes, D. (2025) https://BioRender.com/m39r385.