Background: Canine oral melanoma (COM) is an aggressive and often fatal neoplasm in dogs, with clinical and molecular similarities to human melanoma. Despite its relevance as a comparative oncology model, the molecular mechanisms underlying COM remain poorly understood. This study aimed to characterize gene expression profiles in COM to identify differentially expressed genes (DEGs), potential biomarkers, and therapeutic targets. Methods: In this pilot study, we performed RNA sequencing (RNA-seq) on tumor and healthy oral tissue samples from dogs. Two independent analytical pipelines—Bowtie2-DESeq2 and HISAT-StringTie-Ballgown—were used to ensure robustness in DEG detection. We also conducted pathway enrichment and isoform-level analyses to investigate biological processes and alternative splicing events. Results: Both approaches identified a core set of 929 common DEGs. Key oncogenic pathways, including MAPK/ERK and cell cycle regulation, were significantly affected, with notable upregulation of BRAF, NRAS, CDK4, and MITF (log2FC = 2.86,p< 0.001). The transcription factor SOX10 and the cytokine IL-33, both previously implicated in melanoma progression, were consistently overexpressed. Additionally, NF1, a known RAS pathway inhibitor, was also upregulated. Isoform analysis revealed novel transcript variants, suggesting a complex layer of post-transcriptional regulation in COM. Many DEGs remained uncharacterized, and chromosomal distribution analysis highlighted potential genomic influences. Conclusions: Our findings provide new insights into the molecular landscape of COM, reinforcing its utility as a model for human melanoma. The identification of conserved oncogenic pathways and novel transcript variants opens avenues for further functional studies and the development of targeted therapies in both veterinary and human oncology.
背景：犬口腔黑色素瘤（COM）是一种侵袭性强且常致命的犬类肿瘤，在临床和分子层面与人类黑色素瘤具有相似性。尽管其作为比较肿瘤学模型具有重要意义，但COM的分子机制仍知之甚少。本研究旨在分析COM的基因表达谱，以识别差异表达基因（DEGs）、潜在生物标志物及治疗靶点。 方法：在这项初步研究中，我们对犬的肿瘤组织和健康口腔组织样本进行了RNA测序（RNA-seq）。为确保DEG检测的稳健性，我们采用了两种独立分析流程——Bowtie2-DESeq2和HISAT-StringTie-Ballgown。同时，我们进行了通路富集分析和异构体水平分析，以探究相关生物学过程及可变剪接事件。 结果：两种分析方法共同识别出一组包含929个基因的核心DEGs。关键致癌通路，包括MAPK/ERK通路和细胞周期调控通路，受到显著影响，其中BRAF、NRAS、CDK4和MITF基因显著上调（log2FC = 2.86, p < 0.001）。先前已知与黑色素瘤进展相关的转录因子SOX10和细胞因子IL-33均持续过表达。此外，已知的RAS通路抑制因子NF1也出现上调。异构体分析揭示了新的转录本变异，表明COM中存在复杂的转录后调控层面。许多DEGs的功能尚未明确，染色体分布分析则提示了潜在的基因组影响。 结论：我们的研究结果为COM的分子图谱提供了新见解，进一步证实了其作为人类黑色素瘤模型的价值。保守致癌通路的识别以及新转录本变异的发现，为后续功能研究以及兽医和人类肿瘤学中靶向疗法的开发开辟了新途径。
肿瘤(癌症)患者之家