School of Pharmaceutical Science and Technology, Tianjin University, 300072 Tianjin, China.
Breast Cancer Res Treat. 2010 Jul;122(1):65-75. doi: 10.1007/s10549-009-0505-z. Epub 2009 Sep 2.
Cancer arises from a step-wise accumulation of genetic and epigenetic changes in oncogenes and tumor suppressor genes, followed by changes in transcription and protein profiles. To identify the intrinsic transcriptional features of breast cancer and to explore in more detail the molecular basis of breast carcinogenesis, genes differentially expressed between cancers and their paired normal breast samples in nine breast cancer patients were screened using microarray. Nine normal breast tissues and 49 breast cancer tissue samples were then clustered based on the set of differentially expressed genes. A transcriptional signature of breast cancer consisting of 188 differentially expressed genes was identified. This signature allowed the normal breast tissues to be distinguished from all of the breast cancer samples, and primary breast cancers could be classified into two phenotype-associated subgroups with different ER status and clinical outcome. Furthermore, the classification accuracy of the set of differentially expressed genes was validated in publically available breast microarray data. Moreover, the differentially expressed genes could be grouped into five subclusters involved in different biological processes of carcinogenesis. Most genes in a given subcluster interacted within an independent subnetwork, and subnetworks could cross-talk through a set of signal molecules. Thus, the transcriptional signature identified here may be an intrinsic feature of breast cancer, and it may constitute to the molecular basis of breast carcinogenesis and different phenotypes of breast cancer.
癌症是由癌基因和肿瘤抑制基因的遗传和表观遗传变化的逐步积累引起的，随后是转录和蛋白质谱的变化。为了确定乳腺癌的内在转录特征，并更详细地探讨乳腺癌发生的分子基础，我们使用微阵列筛选了 9 名乳腺癌患者的癌症与其配对正常乳腺样本之间差异表达的基因。然后，根据差异表达基因集对 9 个正常乳腺组织和 49 个乳腺癌组织样本进行聚类。确定了一个由 188 个差异表达基因组成的乳腺癌转录特征。该特征可区分正常乳腺组织和所有乳腺癌样本，并且原发性乳腺癌可以根据不同的 ER 状态和临床结果分为两个与表型相关的亚组。此外，该差异表达基因集的分类准确性在公开的乳腺癌微阵列数据中得到验证。此外，差异表达基因可以分为涉及致癌作用不同生物学过程的五个亚群。给定亚群中的大多数基因在独立的子网络中相互作用，并且子网络可以通过一组信号分子进行交流。因此，这里鉴定的转录特征可能是乳腺癌的内在特征，它可能构成乳腺癌发生和乳腺癌不同表型的分子基础。
