Contaminating cells alter gene signatures in whole organ versus laser capture microdissected tumors: a comparison of experimental breast cancers and their lymph node metastases
Contaminating cells alter gene signatures in whole organ versus laser capture microdissected tumors: a comparison of experimental breast cancers and their lymph node metastases
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DOI：
10.1007/s10585-007-9105-7
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发表时间：
2008-03-01
影响因子：
4
通讯作者：
Horwitz, Kathryn B.
中科院分区：
文献类型：
--
作者：
Harrell, Joshua Chuck;Dye, Wendy W.;Horwitz, Kathryn B.
全基因组表达谱分析加快了我们对乳腺癌不同亚型的分子理解，并确定了原发肿瘤及其转移瘤中表达的基因之间的差异。激光捕获显微切割（LCM）与基因表达分析相结合，使我们能够了解特定细胞类型如何影响总的癌症基因表达特征。表达谱用于定义有助于乳腺癌扩散到引流淋巴结（LN）中和/或在引流淋巴结（LN）内生长的基因。将整个肿瘤异种移植物及其匹配的整个LN转移与LCM捕获的来自相同肿瘤和匹配的LN转移的癌细胞进行比较。仅通过整个器官方法鉴定了1930个基因，仅通过LCM方法鉴定了1,281个基因。然而，不到1%（30个基因）的基因，改变肿瘤和LN转移是共同的两种方法。这些基因中的几个以前与癌症的侵袭性有关。我们的数据表明，全器官和LCM为基础的基因表达谱产生明显不同的列表转移促进基因。肿瘤细胞的污染以及小鼠RNA与人类特异性芯片的交叉反应可能解释了这些差异，并表明LCM衍生的数据可能更准确。
Genome-wide expression profiling has expedited our molecular understanding of the different subtypes of breast cancers, as well as defined the differences among genes expressed in primary tumors and their metastases. Laser-capture microdissection (LCM) coupled to gene expression analysis allows us to understand how specific cell types contribute to the total cancer gene expression signature. Expression profiling was used to define genes that contribute to breast cancer spread into and/or growth within draining lymph nodes (LN). Whole tumor xenografts and their matched whole LN metastases were compared to LCM captured cancer cells from the same tumors and matched LN metastases. One-thousand nine-hundred thirty genes were identified by the whole organ method alone, and 1,281 genes by the LCM method alone. However, less than 1% (30 genes) of genes that changed between tumors and LN metastases were common to both methods. Several of these genes have previously been implicated in cancer aggressiveness. Our data show that whole-organ and LCM based gene expression profiling yield distinctly different lists of metastasis-promoting genes. Contamination of the tumor cells, and cross reactivity of mouse RNA to human-specific chips may explain these differences, and suggests that LCM-derived data may be more accurate.