Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to Human Breast Cancers.

Transcriptome Signatures of Canine Mammary Gland Tumors and Its Comparison to Human Breast Cancers.
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犬乳腺肿瘤的转录组特征及其与人乳腺癌的比较。

DOI:
10.3390/cancers10090317
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发表时间:
2018-09-07
期刊:
影响因子:
5.2
通讯作者:
Cho JY
Cho JY
中科院分区:
医学2区
文献类型:
--
作者:
Lee KH;Park HM;Son KH;Shin TJ;Cho JY

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乳腺癌 (BC)/乳腺癌 (MGC) 是女性和犬科动物中最常诊断出的癌症相关死亡的主要原因。为了更好地了解犬 MGC 和人类 BC 特异性基因,我们对从狗的八对癌组织和邻近正常组织中获得的 RNA 进行了测序。通过全面的转录组分析,在整个犬 MGC 中鉴定出 351 个差异表达基因 (DEG)。基于DEG,比较分析揭示了犬MGC的三种组织学亚型(导管型、简单型和复杂型)与人类BC的四种分子亚型(HER2+、ER+、ER&HER2+和TNBC)之间存在相关性。犬 MGC 的所有三种亚型共有的 8 个 DEG 此前已在人类研究中被报道为癌症相关基因。使用已识别的 DEG 进行基因本体论和通路分析表明,细胞增殖、粘附和炎症反应的生物过程在上调的 MGC DEG 中丰富。相比之下,MGC DEG 中参与细胞命运决定的脂肪酸稳态和转录调控则下调。此外,上游启动子转录物和 DEG 之间的相关性也得到了证明。犬 MGC 和亚型丰富的基因表达使我们能够更好地了解人类 BC 和犬 MGC,从而为这两种疾病的生物标志物和靶标的开发提供新的见解。
Breast cancer (BC)/mammary gland carcinoma (MGC) is the most frequently diagnosed and leading cause of cancer-related mortality in both women and canines. To better understand both canine MGC and human BC-specific genes, we sequenced RNAs obtained from eight pairs of carcinomas and adjacent normal tissues in dogs. By comprehensive transcriptome analysis, 351 differentially expressed genes (DEGs) were identified in overall canine MGCs. Based on the DEGs, comparative analysis revealed correlation existing among the three histological subtypes of canine MGC (ductal, simple, and complex) and four molecular subtypes of human BC (HER2+, ER+, ER&HER2+, and TNBC). Eight DEGs shared by all three subtypes of canine MGCs had been previously reported as cancer-associated genes in human studies. Gene ontology and pathway analyses using the identified DEGs revealed that the biological processes of cell proliferation, adhesion, and inflammatory responses are enriched in up-regulated MGC DEGs. In contrast, fatty acid homeostasis and transcription regulation involved in cell fate commitment were down-regulated in MGC DEGs. Moreover, correlations are demonstrated between upstream promoter transcripts and DEGs. Canine MGC- and subtype-enriched gene expression allows us to better understand both human BC and canine MGC, yielding new insight into the development of biomarkers and targets for both diseases.
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