Tissue transcriptome profiling and pathway analyses revealed novel potential biomarkers in the tumor progression of canine oral melanoma

Abstract

Canine oral melanoma (COM) is an aggressive oral malignancy in dogs, mostly with metastasis. However, the understanding of total gene expression of oral melanoma (OM) at different clinical stages has been limited. The objective of this study was to identify novel mRNA biomarkers of early-stage OM (EOM) and late-stage OM (LOM). Transcriptome sequencing of 3 EOM, 5 LOM and 4 normal gingival tissues (controls) was performed. Selected transcriptome results were validated by quantitative reverse transcription-PCR (qRT-PCR) using 12 LOM and 10 controls. We found 534 differentially expressed in EOM compared with controls, whereas 696 genes in LOM were differentially expressed compared with controls (P < 0.05). Moreover, 27 genes were differentially expressed in LOM compared with EOM (P < 0.05). The genes expressed in COM were involved in the molecular mechanism of cancer and melanocyte development pathways, promoting melanoma progression. qRT-PCR confirmed an increased expression of genes encoding an important protein in chemotherapy resistance (dopachrome tautomerase, DCT) and tumor progression (forkhead box M1, FOXM1), and decreased expression of a tumor suppression gene (N-myc downstream-regulated gene 2, NDRG2) in LOM, concordant with transcriptome results. In conclusion, this study revealed the comprehensive transcriptome from COM tissues, and increased DCT and FOXM1 and decreased NDRG2 gene expression indicated the potential candidate biomarkers in COM progression.

Keywords: Cancer biomarkers; Canine oral melanoma; Dopachrome tautomerase; Forkhead box M1; RNA-Seq; Transcriptome.