Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-modulating stromal components
Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-modulating stromal components
复制标题
DOI：
10.1038/s41598-020-62354-8
复制
发表时间：
2020-03-26
影响因子：
4.6
通讯作者：
Markkanen, Enni
中科院分区：
文献类型：
--
作者：
Amini, Parisa;Nassiri, Sina;Markkanen, Enni
虽然恶性肿瘤中的癌症相关间质（CAS）已得到充分描述，但自然发生的肿瘤良性形式的间质变化仍缺乏特征。自发性犬乳腺癌（mCA）被认为是人类mCA的良好模型。我们最近报道了基于激光捕获显微切割FFPE标本的转录组分析的犬和人mCA之间高度保守的基质重编程。为了确定良性和恶性乳腺肿瘤之间的间质变化，我们分析了13只犬乳腺腺瘤的匹配正常和腺瘤相关间质（AAS），并将其与15只犬mCA的先前数据进行了比较。我们的分析揭示了即使在小的良性肿瘤中也存在明显的基质重编程。虽然AAS和CAS之间存在相似性，但基质特征清楚地将腺瘤与mCA区分开来。AAS和CAS之间的区别进一步证实了差异富集在几个标志性的信号通路，以及差异丰富的细胞组成。最后，我们确定了COL 11 A1，VIT，CD 74，HLA-B1，STRA 6，IGFBP 4，PIGR和TNIP 1作为腺瘤和mCA之间的强区分性基质基因，并证明了它们对人类乳腺癌的预后价值。鉴于犬CAS作为人类疾病模型的相关性，我们的方法确定了对人类和犬乳腺癌都有影响的疾病调节基质成分。
While cancer-associated stroma (CAS) in malignant tumours is well described, stromal changes in benign forms of naturally occurring tumours remain poorly characterized. Spontaneous canine mammary carcinomas (mCA) are viewed as excellent models of human mCA. We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser-capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed matched normal and adenoma-associated stroma (AAS) from 13 canine mammary adenomas and compared them to previous data from 15 canine mCA. Our analyses reveal distinct stromal reprogramming even in small benign tumours. While similarities between AAS and CAS exist, the stromal signature clearly distinguished adenomas from mCA. The distinction between AAS and CAS is further substantiated by differential enrichment in several hallmark signalling pathways as well as differential abundance in cellular composition. Finally, we identify COL11A1, VIT, CD74, HLA-DRA, STRA6, IGFBP4, PIGR, and TNIP1 as strongly discriminatory stromal genes between adenoma and mCA, and demonstrate their prognostic value for human breast cancer. Given the relevance of canine CAS as a model for the human disease, our approach identifies disease-modulating stromal components with implications for both human and canine breast cancer.