Wang Huixia, Huang Shuguang, Shou Jianyong, Su Eric W, Onyia Jude E, Liao Birong, Li Shuyu
Integrative Biology, Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
BMC Genomics. 2006 Jul 3;7:166. doi: 10.1186/1471-2164-7-166.
NCI60 cell lines are derived from cancers of 9 tissue origins and have been invaluable in vitro models for cancer research and anti-cancer drug screen. Although extensive studies have been carried out to assess the molecular features of NCI60 cell lines related to cancer and their sensitivities to more than 100,000 chemical compounds, it remains unclear if and how well these cell lines represent or model their tumor tissues of origin. Identification and confirmation of correct origins of NCI60 cell lines are critical to their usage as model systems and to translate in vitro studies into clinical potentials. Here we report a direct comparison between NCI60 cell lines and primary tumors by analyzing global gene expression profiles.
Comparative analysis suggested that 51 of 59 cell lines we analyzed represent their presumed tumors of origin. Taking advantage of available clinical information of primary tumor samples used to generate gene expression profiling data, we further classified those cell lines with the correct origins into different subtypes of cancer or different stages in cancer development. For example, 6 of 7 non-small cell lung cancer cell lines were classified as lung adenocarcinomas and all of them were classified into late stages in tumor progression.
Taken together, we developed and applied a novel approach for systematic comparative analysis and integrative classification of NCI60 cell lines and primary tumors. Our results could provide guidance to the selection of appropriate cell lines for cancer research and pharmaceutical compound screenings. Moreover, this gene expression profile based approach can be generally applied to evaluate experimental model systems such as cell lines and animal models for human diseases.
NCI60细胞系源自9种组织来源的癌症,是癌症研究和抗癌药物筛选中非常有价值的体外模型。尽管已经进行了广泛的研究来评估NCI60细胞系与癌症相关的分子特征及其对100,000多种化合物的敏感性,但这些细胞系是否以及在多大程度上代表或模拟其起源的肿瘤组织仍不清楚。确定和确认NCI60细胞系的正确起源对于将其用作模型系统以及将体外研究转化为临床应用至关重要。在此,我们通过分析全局基因表达谱报告了NCI60细胞系与原发性肿瘤之间的直接比较。
比较分析表明,我们分析的59个细胞系中有51个代表其假定的起源肿瘤。利用用于生成基因表达谱数据的原发性肿瘤样本的可用临床信息,我们进一步将那些起源正确的细胞系分类为癌症的不同亚型或癌症发展的不同阶段。例如,7个非小细胞肺癌细胞系中有6个被分类为肺腺癌,并且它们全部被分类为肿瘤进展的晚期阶段。
综上所述,我们开发并应用了一种新方法,用于对NCI60细胞系和原发性肿瘤进行系统的比较分析和综合分类。我们的结果可为癌症研究和药物化合物筛选中合适细胞系的选择提供指导。此外,这种基于基因表达谱的方法可普遍应用于评估诸如细胞系和人类疾病动物模型等实验模型系统。