Correlation of gene expression profiles to identify pancreatic cancer cell lines that best model primary human tumors.
Correlation of gene expression profiles to identify pancreatic cancer cell lines that best model primary human tumors.
复制标题
DOI：
10.21037/tcr-23-173
复制
发表时间：
2023-04-28
影响因子：
0.9
通讯作者：
中科院分区：
文献类型：
--
作者：
癌细胞系是研究体内肿瘤生物学的重要研究模型。这些研究的准确性高度依赖于细胞系与患者肿瘤的表型和遗传相似性，但情况并非总是如此，特别是对于胰腺癌。我们比较了各种胰腺癌细胞系和原发性人类胰腺肿瘤组织的基因表达谱，以确定哪种胰腺癌细胞系最适合作为人类原发性肿瘤的模型。从基因表达综合数据库（GEO）获得33个胰腺癌细胞系和892个胰腺癌（PAAD）患者样品的信使RNA（mRNA）表达谱。使用稳健多芯片平均（RMA）算法对微阵列数据进行归一化，并使用ComBat进行批次效应去除。基于具有最大四分位数范围（IQR）的前2，000个基因、134个癌症相关通路的基因集合和504个癌症相关功能的基因集合，使用成对Pearson相关性分析将每个PAAD细胞系的汇总数据与患者肿瘤进行比较。基于前2,000个基因，PAAD细胞系与患者肿瘤组织的相关性很差。高达50%的癌症相关通路在PAAD细胞系中不被强烈推荐，并且一小部分癌症相关功能（12-17%）与PAAD细胞系的相关性很差。在泛途径分析中，显示与患者肿瘤最高遗传相关性的细胞系是来自原发性病变部位的PAAD细胞系的Panc 03.27和来自转移性病变部位的PAAD细胞系的CFPAC-1。在泛功能分析中，显示与患者肿瘤的最高遗传相关性的细胞系是来自原发性病变部位的PAAD细胞系的Panc 03.27和来自转移性病变部位的PAAD细胞系的Capan-1。PAAD细胞系的基因表达谱与原发性胰腺肿瘤的基因表达谱弱相关。通过比较PAAD细胞系与人肿瘤组织的遗传相似性，为选择合适的PAAD细胞系提供了策略。
Cancer cell lines are important research models for studying tumor biology in vivo. The accuracy of such studies is highly dependent on the phenotypic and genetic similarity of cell lines to patient tumors, but this is not always the case, particularly for pancreatic cancer. We compared the gene expression profiles of various pancreatic cancer cell lines and primary human pancreatic tumor tissues to determine which pancreatic cancer cell line best models human primary tumor. Profiles of messenger RNA (mRNA) expression of 33 pancreatic cancer cell lines and 892 patient samples of pancreatic adenocarcinoma (PAAD) were obtained from the Gene Expression Omnibus (GEO) database. Microarray data were normalized using the robust multichip average (RMA) algorithm and batch effect removal was performed using ComBat. The pooled data of each PAAD cell line were compared to patient tumors based on the top 2,000 genes with largest interquartile range (IQR), 134 gene-collections of cancer-related pathways, and 504 gene-collections of cancer-related functions using pairwise Pearson’s correlation analysis. PAAD cell lines were poorly correlated with patient tumor tissues based on the top 2,000 genes. Up to 50% of cancer-related pathways were not strongly recommended in PAAD cell lines, and a small proportion of cancer-related functions (12–17%) were poorly correlated with PAAD cell lines. In pan-pathway analysis, the cell lines showing the highest genetic correlation to patient tumors were Panc 03.27 for PAAD cell lines from a primary lesion site and CFPAC-1 for PAAD cell lines from a metastatic lesion site. In pan-function analysis, the cell lines showing the highest genetic correlation to patient tumors were Panc 03.27 for PAAD cell lines from a primary lesion site and Capan-1 for PAAD cell lines from a metastatic lesion site. The gene expression profiles of PAAD cell lines correlate weakly with those of primary pancreatic tumors. Through comparison of the genetic similarity between PAAD cell lines and human tumor tissue, we have provided a strategy for choosing the appropriate PAAD cell line.
影响因子：
--
作者：
Tataranni T;Agriesti F;Ruggieri V;Mazzoccoli C;Simeon V;Laurenzana I;Scrima R;Pazienza V;Capitanio N;Piccoli C
通讯作者：
Piccoli C