Department of Veterinary Surgery, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence for Companion Animal Cancer, Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand.
Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L69 3BX, United Kingdom.
Res Vet Sci. 2023 Dec;165:105036. doi: 10.1016/j.rvsc.2023.105036. Epub 2023 Oct 2.
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.
犬口腔黑色素瘤 (COM) 是一种侵袭性犬口腔恶性肿瘤，多伴有转移。然而，对于不同临床阶段口腔黑色素瘤 (OM) 的整体基因表达的理解仍有限。本研究旨在鉴定早期 OM (EOM) 和晚期 OM (LOM) 的新型 mRNA 生物标志物。对 3 例 EOM、5 例 LOM 和 4 例正常牙龈组织（对照）进行转录组测序。通过定量逆转录 PCR (qRT-PCR) 使用 12 例 LOM 和 10 例对照验证了选定的转录组结果。与对照相比，我们发现 EOM 中有 534 个基因差异表达，而 LOM 中有 696 个基因差异表达（P < 0.05）。此外，LOM 与 EOM 相比有 27 个基因差异表达（P < 0.05）。在 COM 中表达的基因参与癌症和黑素细胞发育途径的分子机制，促进黑色素瘤的进展。qRT-PCR 证实了编码化疗耐药（多巴色素互变异构酶，DCT）和肿瘤进展（叉头框 M1，FOXM1）重要蛋白的基因表达增加，以及肿瘤抑制基因（N- MYC 下游调节基因 2，NDRG2）表达减少，与转录组结果一致。总之，本研究揭示了 COM 组织的全面转录组，DCT、FOXM1 表达增加和 NDRG2 基因表达减少表明了 COM 进展中的潜在候选生物标志物。
