Tran Vy, Kim Robert, Maertens Mikhail, Hartung Thomas, Maertens Alexandra
Department of Environmental Health and Engineering, Center for Alternatives to Animal Testing, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United States.
Department of Biology, Center for Alternatives to Animal Testing-Europe, University of Konstanz, Konstanz, Germany.
Front Artif Intell. 2021 May 13;4:674370. doi: 10.3389/frai.2021.674370. eCollection 2021.
Failure to adequately characterize cell lines, and understand the differences between and biology, can have serious consequences on the translatability of scientific studies to human clinical trials. This project focuses on the Michigan Cancer Foundation-7 (MCF-7) cells, a human breast adenocarcinoma cell line that is commonly used for cancer research, with over 42,000 publications in PubMed. In this study, we explore the key similarities and differences in gene expression networks of MCF-7 cell lines compared to human breast cancer tissues. We used two MCF-7 data sets, one data set collected by ARCHS4 including 1032 samples and one data set from Gene Expression Omnibus GSE50705 with 88 estradiol-treated MCF-7 samples. The human breast invasive ductal carcinoma (BRCA) data set came from The Cancer Genome Atlas, including 1212 breast tissue samples. Weighted Gene Correlation Network Analysis (WGCNA) and functional annotations of the data showed that MCF-7 cells and human breast tissues have only minimal similarity in biological processes, although some fundamental functions, such as cell cycle, are conserved. Scaled connectivity-a network topology metric-also showed drastic differences in the behavior of genes between MCF-7 and BRCA data sets. Finally, we used canSAR to compute ligand-based druggability scores of genes in the data sets, and our results suggested that using MCF-7 to study breast cancer may lead to missing important gene targets. Our comparison of the networks of MCF-7 and human breast cancer highlights the nuances of using MCF-7 to study human breast cancer and can contribute to better experimental design and result interpretation of study involving this cell line.
未能充分表征细胞系并理解其生物学差异，可能会对科学研究向人类临床试验的可转化性产生严重影响。本项目聚焦于密歇根癌症基金会-7（MCF-7）细胞，这是一种常用于癌症研究的人乳腺腺癌细胞系，在PubMed上有超过42000篇相关出版物。在本研究中，我们探讨了MCF-7细胞系与人类乳腺癌组织相比，基因表达网络中的关键异同。我们使用了两个MCF-7数据集，一个由ARCHS4收集的包含1032个样本的数据集，以及一个来自基因表达综合数据库GSE50705的包含88个经雌二醇处理的MCF-7样本的数据集。人类乳腺浸润性导管癌（BRCA）数据集来自癌症基因组图谱，包含1212个乳腺组织样本。加权基因共表达网络分析（WGCNA）和数据的功能注释表明，MCF-7细胞与人类乳腺组织在生物学过程中仅有极小的相似性，尽管一些基本功能，如细胞周期，是保守的。缩放连通性——一种网络拓扑指标——也显示了MCF-7和BRCA数据集之间基因行为的巨大差异。最后，我们使用canSAR计算数据集中基因基于配体的成药可能性得分，我们的结果表明，使用MCF-7研究乳腺癌可能会遗漏重要的基因靶点。我们对MCF-7和人类乳腺癌网络的比较突出了使用MCF-7研究人类乳腺癌的细微差别，并有助于更好地设计涉及该细胞系的实验以及解释研究结果。
