A Whole-Transcriptomic Analysis of Canine Oral Melanoma: A Chance to Disclose the Radiotherapy Effect and Outcome-Associated Gene Signature

Abstract

Oral melanoma (OM) is the most common malignant oral tumour among dogs and shares similarities with human mucosal melanoma (HMM), validating the role of canine species as an immunocompetent model for cancer research. In both humans and dogs, the prognosis is poor and radiotherapy (RT) represents a cornerstone in the management of this tumour, either as an adjuvant or a palliative treatment. In this study, by means of RNA-seq, the effect of RT weekly fractionated in 9 Gray (Gy), up to a total dose of 36 Gy (4 weeks), was evaluated in eight dogs affected by OM. Furthermore, possible transcriptomic differences in blood and biopsies that might be associated with a longer overall survival (OS) were investigated. The immune response, glycosylation, cell adhesion, and cell cycle were the most affected pathways by RT, while tumour microenvironment (TME) composition and canonical and non-canonical WNT pathways appeared to be modulated in association with OS. Taking these results as a whole, this study improved our understanding of the local and systemic effect of RT, reinforcing the pivotal role of anti-tumour immunity in the control of canine oral melanoma (COM).

Keywords: RNA-seq; dog; melanoma; radiotherapy; temozolomide.

Figure 1

A ridgeplot of the 25 most significant terms as results of GSEA comparing tumour T1 vs. T0. The colour gradient is related to the level of significance, adjusted with the Benjamini–Hochberg method.

Figure 2

A dotplot of GSEA results comparing blood T1 vs. T0. The dot size represents the number of genes belonging to each pathway. The colour gradient is related to the level of significance, adjusted with the Benjamini–Hochberg method. The box on the left collects activated pathways, while the box on the right collects suppressed ones.