Liu Li-Yu Daisy, Chang Li-Yun, Kuo Wen-Hung, Hwa Hsiao-Lin, Lin Yi-Shing, Huang Shiu-Feng, Chen Chiung-Nien, Chang King-Jen, Hsieh Fon-Jou
Department of Agronomy, Biometry Division, National Taiwan University, Taipei, Taiwan.
Cancer Inform. 2012;11:87-111. doi: 10.4137/CIN.S8633. Epub 2012 Apr 19.
We aimed to find clinically relevant gene activities ruled by the signal transducer and activator of transcription 3 (STAT3) proteins in an ER(-) breast cancer population via network approach. STAT3 is negatively associated with both lymph nodal category and stage. MYC is a component of STAT3 network. MYC and STAT3 may co-regulate gene expressions for Warburg effect, stem cell like phenotype, cell proliferation and angiogenesis. We identified a STAT3 network in silico showing its ability in predicting its target gene expressions primarily for specific tumor subtype, tumor progression, treatment options and prognostic features. The aberrant expressions of MYC and STAT3 are enriched in triple negatives (TN). They promote histological grade, vascularity, metastasis and tumor anti-apoptotic activities. VEGFA, STAT3, FOXM1 and METAP2 are druggable targets. High levels of METAP2, MMP7, IGF2 and IGF2R are unfavorable prognostic factors. STAT3 is an inferred center regulator at early cancer development predominantly in TN.
我们旨在通过网络方法，在雌激素受体阴性（ER(-)）乳腺癌人群中找出由信号转导子和转录激活子3（STAT3）蛋白调控的临床相关基因活性。STAT3与淋巴结分类和分期均呈负相关。MYC是STAT3网络的一个组成部分。MYC和STAT3可能共同调节与瓦伯格效应、干细胞样表型、细胞增殖和血管生成相关的基因表达。我们在计算机模拟中识别出一个STAT3网络，显示其能够主要针对特定肿瘤亚型、肿瘤进展、治疗方案和预后特征预测其靶基因表达。MYC和STAT3的异常表达在三阴性（TN）乳腺癌中富集。它们促进组织学分级、血管生成、转移和肿瘤抗凋亡活性。血管内皮生长因子A（VEGFA）、STAT3、叉头框蛋白M1（FOXM1）和金属蛋白酶2（METAP2）是可成药靶点。METAP2、基质金属蛋白酶7（MMP7）、胰岛素样生长因子2（IGF2）和胰岛素样生长因子2受体（IGF2R）水平高是不良预后因素。STAT3是癌症早期发展中主要在三阴性乳腺癌中的一个推断的中心调节因子。
