Lineberger Comprehensive Cancer Center, University of North Carolina, 450 West Drive, CB7295, Chapel Hill, NC 27599, USA.
Breast Cancer Res Treat. 2012 Apr;132(2):523-35. doi: 10.1007/s10549-011-1619-7. Epub 2011 Jun 14.
The ability to predict metastatic potential could be of great clinical importance, however, it is uncertain if predicting metastasis to specific vital organs is feasible. As a first step in evaluating metastatic predictions, we analyzed multiple primary tumors and metastasis pairs and determined that >90% of 298 gene expression signatures were found to be similarly expressed between matched pairs of tumors and metastases; therefore, primary tumors may be a good predictor of metastatic propensity. Next, using a dataset of >1,000 human breast tumor gene expression microarrays we determined that HER2-enriched subtype tumors aggressively spread to the liver, while basal-like and claudin-low subtypes colonize the brain and lung. Correspondingly, brain and lung metastasis signatures, along with embryonic stem cell, tumor initiating cell, and hypoxia signatures, were also strongly expressed in the basal-like and claudin-low tumors. Interestingly, low "Differentiation Scores," or high expression of the aforementioned signatures, further predicted for brain and lung metastases. In total, these data identify that depending upon the organ of relapse, a combination of gene expression signatures most accurately predicts metastatic behavior.
预测转移潜能可能具有重要的临床意义，然而，预测转移至特定重要器官是否可行尚不确定。作为评估转移预测的第一步，我们分析了多个原发肿瘤和转移对，并确定在肿瘤和转移的匹配对之间，>90%的 298 个基因表达特征被发现具有相似的表达；因此，原发肿瘤可能是转移倾向的良好预测指标。接下来，我们使用超过 1000 个人类乳腺癌肿瘤基因表达微阵列数据集，确定了 HER2 富集亚型肿瘤会积极转移到肝脏，而基底样和 Claudin-low 亚型则会在大脑和肺部定植。相应地，脑和肺转移特征，以及胚胎干细胞、肿瘤起始细胞和缺氧特征，在基底样和 Claudin-low 肿瘤中也强烈表达。有趣的是，低的“分化评分”或上述特征的高表达，进一步预测了脑和肺转移。总的来说，这些数据表明，根据复发器官的不同，组合基因表达特征最能准确预测转移行为。
