Omics-based profiling of carcinoma of the breast and matched regional lymph node metastasis
Omics-based profiling of carcinoma of the breast and matched regional lymph node metastasis
复制标题
DOI：
10.1002/pmic.200800303
复制
发表时间：
2008-12-01
期刊：
影响因子：
3.4
通讯作者：
Celis, Julio E.
中科院分区：
文献类型：
--
作者：
Li, Jian;Gromov, Pavel;Celis, Julio E.
腋窝淋巴结（ALN）状态目前被用作乳腺癌预后的重要临床指标。然而，淋巴结转移的分子机制知之甚少，ALN转移和原发肿瘤之间的关系仍然不清楚。为了揭示基因组的结构变化和相关的蛋白质反应，可能会推动区域转移进展，我们分析了匹配对原发性乳腺肿瘤和ALN转移，在基因组和蛋白质组水平上使用比较基因组杂交（CGH）阵列，定量高分辨率2-D PAGE结合MS，免疫组化（IHC）。阵列CGH显示匹配的原发肿瘤和ALN转移瘤之间的基因组畸变谱具有显著的相似性。对135种已知蛋白质的定量分析也揭示了它们的总体表达模式的惊人相似性，尽管我们在一些样品对中观察到单个蛋白质水平的明显变化。原发性肿瘤和匹配的ALN转移瘤之间的总体基因组和蛋白质组谱的显著相似性表明，一般而言，原发性乳腺肿瘤的关键生物学特征在相应的淋巴结转移瘤中得以维持。鉴于基于组学的技术对仅发生在次要细胞亚群中的变化不敏感，我们使用IHC验证了蛋白质组学数据，其提供了具有有价值的拓扑成分的蛋白质表达信息。除了证实组学来源的数据外，IHC分析还显示，在两种情况下，ALN转移可能来源于原发性肿瘤中存在的不同的小细胞亚群，而不是来源于大部分肿瘤。
Axillary lymph node (ALN) status is currently used as an important clinical indicator of breast cancer prognosis. However, the molecular mechanisms underlying lymph node metastasis are poorly understood and the relationship between ALN metastasis and the primary tumor remains unclear. In an effort to reveal structural changes in the genome and related protein responses that may drive regional metastatic progression we have analyzed matched pairs of primary breast tumors and ALN metastases both at the genomic and proteomic levels using comparative genomic hybridization (CGH) array, quantitative high-resolution 2-D PAGE in combination with MS, and immunohistochemistry (IHC). Array CGH revealed a remarkable similarity in genomic aberration profiles between the matched primary tumors and the ALN metastases. Quantitative profiling of 135 known proteins also revealed striking similarities in their overall expression patterns, although we observed distinct changes in the levels of individual proteins in some sample pairs. The remarkable similarities of the overall genomic and proteomic profiles between primary tumors and matched ALN metastases are taken to suggest that, in general, key biological characteristics of the primary breast tumor are maintained in the corresponding lymph node metastases. Given that the omics-based technologies are oblivious to changes that only occur in minor cellular subsets we validated the proteomic data using IHC, which provides protein expression information with a valuable topological component. Besides confirming the omics-derived data, the IHC analysis revealed that in two cases the ALN metastases may have been derived from a distinct minor cell subpopulation present in the primary tumor rather than from the bulk of it.