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Comparative expression pathway analysis of human and canine mammary tumors

机译：人和犬乳腺肿瘤的比较表达途径分析

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Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.
机译：背景技术已证明狗中的自发性肿瘤与人类的自发性肿瘤具有许多特征，包括相关的分子靶标，组织学外观，遗传学，生物学行为以及对常规治疗的反应。因此，狗中的乳腺肿瘤为人为诱发肿瘤的更经典的小鼠模型（如转基因或异种移植）提供了有吸引力的替代方法。为了评估狗肿瘤代表临床上重要的人类表型的程度，我们对这两种物种的乳腺肿瘤中发生的转录变化进行了首次全基因组范围的比较分析，特别关注所涉及的分子途径。结果我们分析了人和狗从肿瘤和正常乳腺样品中得到的基因表达数据。通过分析约一万条狗/人直系同源基因的表达水平，我们观察到与正常小鼠相比，乳腺肿瘤样品中被失调的基因有明显的重叠。基因表达数据的途径分析显示，在许多与癌症相关的途径（包括“ PI3K / AKT”，“ KRAS”，“ PTEN”，“ WNT-beta catenin”和“ MAPK级联”）的扰动中，相似度很高。此外，我们表明，在人类乳腺癌中观察到的不同基因特征之间的转录关系在犬模型中得到了很大的维持，这表明癌症信号传导网络中的种间相似性相似。结论我们的数据证实并进一步增强了犬乳癌模型的价值，并为评估新型癌症疗法以及开发可用于临床研究的预后和诊断生物标志物开辟了新的前景。

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