Comparative Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Preclinical Innovation, Therapeutic Development Branch, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Commun Biol. 2023 Aug 17;6(1):856. doi: 10.1038/s42003-023-05208-z.
Canine osteosarcoma is increasingly recognized as an informative model for human osteosarcoma. Here we show in one of the largest clinically annotated canine osteosarcoma transcriptional datasets that two previously reported, as well as de novo gene signatures devised through single sample Gene Set Enrichment Analysis (ssGSEA), have prognostic utility in both human and canine patients. Shared molecular pathway alterations are seen in immune cell signaling and activation including TH1 and TH2 signaling, interferon signaling, and inflammatory responses. Virtual cell sorting to estimate immune cell populations within canine and human tumors showed similar trends, predominantly for macrophages and CD8+ T cells. Immunohistochemical staining verified the increased presence of immune cells in tumors exhibiting immune gene enrichment. Collectively these findings further validate naturally occurring osteosarcoma of the pet dog as a translationally relevant patient model for humans and improve our understanding of the immunologic and genomic landscape of the disease in both species.
犬骨肉瘤越来越被认为是人类骨肉瘤的一个有价值的模型。在这里，我们在一个最大的临床注释的犬骨肉瘤转录组数据集之一中表明，两个之前报道的以及通过单样本基因集富集分析（ssGSEA）设计的新基因特征，在人类和犬科患者中都具有预后效用。在免疫细胞信号转导和激活中观察到共同的分子途径改变，包括 TH1 和 TH2 信号转导、干扰素信号转导和炎症反应。虚拟细胞分选估计犬科和人类肿瘤中的免疫细胞群体显示出相似的趋势，主要是巨噬细胞和 CD8+T 细胞。免疫组织化学染色证实，在表现出免疫基因富集的肿瘤中，免疫细胞的存在增加。这些发现共同进一步验证了宠物犬的自然发生骨肉瘤作为人类具有转化相关性的患者模型，并提高了我们对两种物种疾病的免疫学和基因组景观的理解。
