Division of Integrative Omics and Bioinformatics, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
PLoS One. 2011 Apr 21;6(4):e18196. doi: 10.1371/journal.pone.0018196.
Surgical samples have long been used as important subjects for cancer research. In accordance with an increase of neoadjuvant therapy, biopsy samples have recently become imperative for cancer transcriptome. On the other hand, both biopsy and surgical samples are available for expression profiling for predicting clinical outcome by adjuvant therapy; however, it is still unclear whether surgical sample expression profiles are useful for prediction via biopsy samples, because little has been done about comparative gene expression profiling between the two kinds of samples.
A total of 166 samples (77 biopsy and 89 surgical) of normal and malignant lesions of the esophagus were analyzed by microarrays. Gene expression profiles were compared between biopsy and surgical samples. Artificially induced epithelial-mesenchymal transition (aiEMT) was found in the surgical samples, and also occurred in mouse esophageal epithelial cell layers under an ischemic condition. Identification of clinically significant subgroups was thought to be disrupted by the disorder of the expression profile through this aiEMT.
This study will evoke the fundamental misinterpretation including underestimation of the prognostic evaluation power of markers by overestimation of EMT IN past cancer research, and will furnish some advice for the near future as follows: 1) Understanding how long the tissues were under an ischemic condition. 2) Prevalence of biopsy samples for in vivo expression profiling with low biases on basic and clinical research. 3) Checking cancer cell contents and normal- or necrotic-tissue contamination in biopsy samples for prevalence.
外科样本一直以来都是癌症研究的重要对象。随着新辅助治疗的增加，活检样本最近也成为癌症转录组学的必要样本。另一方面，活检和手术样本都可用于通过辅助治疗进行表达谱分析，以预测临床结果；然而，由于关于两种样本之间的比较基因表达谱的研究很少，因此尚不清楚手术样本的表达谱是否可用于通过活检样本进行预测。
总共分析了 166 个食管正常和恶性病变的样本（77 个活检和 89 个手术），采用微阵列技术。比较了活检和手术样本之间的基因表达谱。在手术样本中发现了人工诱导的上皮-间充质转化（aiEMT），并且在缺血条件下，在小鼠食管上皮细胞层中也发生了这种转化。通过这种 aiEMT ，认为对表达谱的紊乱会破坏对临床有意义亚组的识别。
这项研究将引起基本的误解，包括在过去的癌症研究中，通过高估 EMT 来低估标志物预后评估能力的错误，并且将为未来的研究提供一些建议：1）了解组织在缺血条件下的持续时间。2）在基础和临床研究中，使用低偏差的活检样本进行体内表达谱分析的流行。3）检查活检样本中癌细胞含量和正常或坏死组织污染情况。
