Fertig Elana J, Lee Esak, Pandey Niranjan B, Popel Aleksander S
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sci Rep. 2015 Jul 15;5:12133. doi: 10.1038/srep12133.
Breast cancer is a heterogeneous disease, having multiple subtypes with different malignant phenotypes. The triple-negative breast cancer, or basal breast cancer, is highly aggressive, metastatic, and difficult to treat. Previously, we identified that key molecules (IL6, CSF2, CCL5, VEGFA, and VEGFC) secreted by tumor cells and stromal cells in basal breast cancer can promote metastasis. It remains to assess whether these molecules function similarly in other subtypes of breast cancer. Here, we characterize the relative gene expression of the five secreted molecules and their associated receptors (GP130, GMRA, GMRB, CCR5, VEGFR2, NRP1, VEGFR3, NRP2) in the basal, HER2 (human epidermal growth factor receptor 2) positive, luminal A, and luminal B subtypes using high throughput data from tumor samples in The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). IL6 and CCL5 gene expression are basal breast cancer specific, whereas high gene expression of GP130 was observed in luminal A/B. VEGFA/C and CSF2 mRNA are overexpressed in HER2 positive breast cancer, with VEGFA and CSF2 also overexpressed in basal breast cancer. Further study of the specific protein function of these factors within their associated cancer subtypes may yield personalized biomarkers and treatment modalities.
乳腺癌是一种异质性疾病,有多种具有不同恶性表型的亚型。三阴性乳腺癌,即基底样乳腺癌,具有高度侵袭性、转移性且难以治疗。此前,我们发现基底样乳腺癌中肿瘤细胞和基质细胞分泌的关键分子(IL6、CSF2、CCL5、VEGFA和VEGFC)可促进转移。这些分子在其他乳腺癌亚型中是否发挥类似作用仍有待评估。在此,我们利用来自癌症基因组图谱(TCGA)和国际乳腺癌分子分类联盟(METABRIC)肿瘤样本的高通量数据,对基底样、HER2(人表皮生长因子受体2)阳性、腔面A型和腔面B型亚型中这五种分泌分子及其相关受体(GP130、GMRA、GMRB、CCR5、VEGFR2、NRP1、VEGFR3、NRP2)的相对基因表达进行了表征。IL6和CCL5基因表达具有基底样乳腺癌特异性,而在腔面A型/ B型中观察到GP130基因高表达。VEGFA/C和CSF2 mRNA在HER2阳性乳腺癌中过表达,VEGFA和CSF2在基底样乳腺癌中也过表达。对这些因子在其相关癌症亚型内的特定蛋白质功能进行进一步研究,可能会产生个性化的生物标志物和治疗方式。