Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer.
Biological functions of the genes in the mammaprint breast cancer profile reflect the hallmarks of cancer.
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DOI：
10.4137/bmi.s6184
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发表时间：
2010-11-28
影响因子：
3.8
通讯作者：
Glas AM
中科院分区：
文献类型：
--
作者：
Tian S;Roepman P;Van't Veer LJ;Bernards R;de Snoo F;Glas AM
MammaPrint被开发为一种诊断工具，使用70个基因的表达来预测乳腺癌转移的风险。为了更好地理解MammaPrint评估的肿瘤生物学，我们解释了70个基因的生物学功能，并展示了基因如何反映Hanahan和温伯格定义的癌症的六个特征。我们使用自下而上的系统生物学方法来阐明70个基因所反映的细胞过程如何共同调节肿瘤活动和进展。利用文献研究和多种生物信息学工具分析了这些基因的生物学功能。蛋白质-蛋白质相互作用网络分析表明，70个基因形成高度互连的网络，并且它们的表达水平受到关键肿瘤发生相关基因如TP 53、RB 1、MYC、JUN和CDKN 2A的调控。这些基因的生物学功能可能与肿瘤进展和转移所必需的基本步骤相关，并涵盖了癌症的六个明确定义的标志，反映了癌细胞的获得性恶性特征沿着肿瘤进展和转移相关的生物学活性。MammaPrint基因签名中的基因全面衡量癌症相关生物学的六个标志。这一发现建立了分子特征与肿瘤细胞进展和转移的潜在分子机制之间的联系。
MammaPrint was developed as a diagnostic tool to predict risk of breast cancer metastasis using the expression of 70 genes. To better understand the tumor biology assessed by MammaPrint, we interpreted the biological functions of the 70-genes and showed how the genes reflect the six hallmarks of cancer as defined by Hanahan and Weinberg. We used a bottom-up system biology approach to elucidate how the cellular processes reflected by the 70-genes work together to regulate tumor activities and progression. The biological functions of the genes were analyzed using literature research and several bioinformatics tools. Protein-protein interaction network analyses indicated that the 70-genes form highly interconnected networks and that their expression levels are regulated by key tumorigenesis related genes such as TP53, RB1, MYC, JUN and CDKN2A. The biological functions of the genes could be associated with the essential steps necessary for tumor progression and metastasis, and cover the six well-defined hallmarks of cancer, reflecting the acquired malignant characteristics of a cancer cell along with tumor progression and metastasis-related biological activities. Genes in the MammaPrint gene signature comprehensively measure the six hallmarks of cancer-related biology. This finding establishes a link between a molecular signature and the underlying molecular mechanisms of tumor cell progression and metastasis.