Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Big Data Research Institute, China Pharmaceutical University, Nanjing, China; Institute of Food Science and Technology, Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka, Bangladesh.
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China; Big Data Research Institute, China Pharmaceutical University, Nanjing, China.
Clin Breast Cancer. 2022 Aug;22(6):521-537. doi: 10.1016/j.clbc.2022.04.001. Epub 2022 Apr 5.
Tumor stroma is a heterogeneous cellular component in the tumor microenvironment of breast cancer. However, very few studies have explored the identification of breast cancer subtypes based on highly heterogeneous tumor stromal signatures.
Using a combined dataset composed of 8 gene expression profiling datasets for breast tumor stroma, we clustered breast cancers based on the expression levels of 100 genes whose expression values were most variable across all samples. Furthermore, we investigated the molecular features of the breast cancer subtypes identified.
We identified 2 breast cancer subtypes, termed SBCS-1 and SBCS-2. We found that the contents of stroma and immune cells were lower in SBCS-1 than in SBCS-2, while the proportion of tumor cells was higher in SBCS-1. SBCS-1 was enriched in cancer-associated pathways, including ribosomes, cell cycle, RNA degradation, RNA polymerase, DNA replication, oxidative phosphorylation, proteasome, spliceosome, and glycolysis/gluconeogenesis. SBCS-2 was enriched in pathways of graft versus host disease, type 1 diabetes mellitus, intestinal immune network for IgA production, allograft rejection, and steroid hormone biosynthesis. Moreover, many oncogenic biological processes were highly activated in SBCS-1, including proliferation, stemness, epithelial-to-mesenchymal transition (EMT), and angiogenesis. Gene co-expression network analysis identified prognostic hub genes, transcription factor encoding genes (PFDN5 and EZH2), and protein kinase encoding gene (AURKA) in a gene module highly enriched in SBCS-1.
Based on the gene expression profiles in breast cancer stroma, breast cancer can be divided into 2 subtypes, which have significantly different molecular, and clinical characteristics. The identification of new subtypes of breast cancer has clinical implications for the management of this disease.
肿瘤基质是乳腺癌肿瘤微环境中的一种异质细胞成分。然而，很少有研究基于高度异质性的肿瘤基质特征来鉴定乳腺癌亚型。
我们使用由 8 个乳腺癌肿瘤基质基因表达谱数据集组成的组合数据集，根据在所有样本中表达值变化最大的 100 个基因的表达水平对乳腺癌进行聚类。此外，我们还研究了鉴定出的乳腺癌亚型的分子特征。
我们鉴定出了 2 种乳腺癌亚型，分别称为 SBCS-1 和 SBCS-2。我们发现 SBCS-1 中的基质和免疫细胞含量低于 SBCS-2，而 SBCS-1 中的肿瘤细胞比例较高。SBCS-1 富集在癌症相关通路中，包括核糖体、细胞周期、RNA 降解、RNA 聚合酶、DNA 复制、氧化磷酸化、蛋白酶体、剪接体和糖酵解/糖异生。SBCS-2 富集在移植物抗宿主病、1 型糖尿病、肠道免疫网络 IgA 产生、同种异体排斥和类固醇激素生物合成途径中。此外，许多致癌生物学过程在 SBCS-1 中高度激活，包括增殖、干性、上皮间质转化（EMT）和血管生成。基因共表达网络分析在一个在 SBCS-1 中高度富集的基因模块中鉴定出了预后关键基因、转录因子编码基因（PFDN5 和 EZH2）和蛋白激酶编码基因（AURKA）。
基于乳腺癌基质中的基因表达谱，乳腺癌可分为 2 种亚型，它们具有显著不同的分子和临床特征。鉴定出新的乳腺癌亚型对这种疾病的治疗具有临床意义。
