犬骨肉瘤的转录谱分析鉴定出预后基因表达特征,具有对人类转化价值的意义。
Transcriptional profiling of canine osteosarcoma identifies prognostic gene expression signatures with translational value for humans.
发表日期:2023 Aug 17
作者:
Joshua D Mannheimer, Gregory Tawa, David Gerhold, John Braisted, Carly M Sayers, Troy A McEachron, Paul Meltzer, Christina Mazcko, Jessica A Beck, Amy K LeBlanc
来源:
Immunity & Ageing
摘要:
犬骨肉瘤越来越被认识为人类骨肉瘤的信息模型。在我们这里,我们展示了最大的临床注释的犬骨肉瘤转录数据集之一,证明了之前报道的两个以及通过单样本基因集富集分析(ssGSEA)制定的全新基因签名在人类和犬类患者中具有预后效用。在免疫细胞信号和活化方面,我们观察到共同的分子通路改变,包括TH1和TH2信号传导、干扰素信号传导和炎症反应。通过虚拟细胞分选来估计犬类和人类肿瘤中的免疫细胞群体,显示出类似的趋势,主要是巨噬细胞和CD8+ T细胞。免疫组织化学染色验证了在免疫基因富集的肿瘤中免疫细胞的增加存在。总的来说,这些发现进一步验证了宠物犬自发性骨肉瘤作为与人类相关的转化患者模型,并提高了我们对该疾病在两个物种中免疫和基因组景观的理解。 © 2023. Springer Nature Limited.
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.© 2023. Springer Nature Limited.