Relating hepatocellular carcinoma tumor samples and cell lines using gene expression data in translational research.

Relating hepatocellular carcinoma tumor samples and cell lines using gene expression data in translational research.
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DOI:
10.1186/1755-8794-8-s2-s5
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发表时间:
2015
影响因子:
2.7
通讯作者:
Butte AJ
Butte AJ
中科院分区:
医学3区
文献类型:
--
作者:
Chen B;Sirota M;Fan-Minogue H;Hadley D;Butte AJ

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癌细胞系被广泛用于研究癌症生物学和测试转化研究中的假设。细胞系的相关性取决于它们与正在研究的肿瘤的相似程度。因此,将肿瘤和细胞系联系起来,并认识到它们的相似性和差异性对于转化研究非常重要。基因组学的快速发展已经导致产生了大量的基因组和转录组数据的原发性癌症样品,正常组织样品和癌细胞系的不同集合。肝细胞癌(HCC)是世界上最常见的肿瘤之一,在亚洲和撒哈拉以南地区发病率较高。目前HCC的有效治疗仍然有限。在这项工作中,我们比较了来自癌症基因组图谱的200个HCC肿瘤样本和来自癌细胞系百科全书的1000多个癌细胞系(包括25个HCC癌细胞系)的基因表达测量。我们表明,与来自其他肿瘤类型的细胞系相比,HCC肿瘤样品与HCC细胞系密切相关。我们进一步证明了最常用的HCC细胞系类似于HCC肿瘤,而我们鉴定了近一半的细胞系不类似于原发性肿瘤。有趣的是,大量对疾病发展或药物反应至关重要的基因在高度相关的细胞系中以低水平表达或不表达;在翻译研究中应额外关注这些基因。我们的研究将用于指导肝癌细胞系的选择,并确定在肿瘤或细胞系中差异表达的特定基因。
Cancer cell lines are used extensively to study cancer biology and to test hypotheses in translational research. The relevance of cell lines is dependent on how closely they resemble the tumors being studied. Relating tumors and cell lines, and recognizing their similarities and differences are thus very important for translational research. Rapid advances in genomics have led to the generation of large volumes of genomic and transcriptomic data for a diverse set of primary cancer samples, normal tissue samples and cancer cell lines. Hepatocellular Carcinoma (HCC) is one of the most common tumors worldwide, with high occurrence in Asia and sub-Saharan regions. The current effective treatments of HCC remain limited. In this work, we compared the gene expression measurements of 200 HCC tumor samples from The Cancer Genome Atlas and over 1000 cancer cell lines including 25 HCC cancer cell lines from Cancer Cell Line Encyclopedia. We showed that the HCC tumor samples correlate closely with HCC cell lines in comparison to cell lines derived from other tumor types. We further demonstrated that the most commonly used HCC cell lines resemble HCC tumors, while we identified nearly half of the cell lines that do not resemble primary tumors. Interestingly, a substantial number of genes that are critical for disease development or drug response are either expressed at low levels or absent among highly correlated cell lines; additional attention should be paid to these genes in translational research. Our study will be used to guide the selection of HCC cell lines and pinpoint the specific genes that are differentially expressed in either tumors or cell lines.