卵巢癌干细胞基因表达谱共有特征分析

Analysis of shared characteristics of ovarian cancer stem cell by gene expression profiling

目的分析卵巢癌干细胞共有的差异基因表达特征。方法将NCBI GEO数据库中获取的细胞系及患者来源的卵巢癌干细胞与各非干性癌细胞的全基因组表达谱进行整合比对分析,运用GeneSifter软件解析出卵巢癌干细胞共有差异表达基因,并对其共同涉及的生物学特性及信号通路进行富集分析。结果卵巢癌IGROV1细胞系和进展期患者腹水来源的干性侧群细胞相比各非干性侧群细胞,以及OVCAR3细胞系来源的多细胞球相比其他非干性卵巢癌细胞的差异表达基因数分别为1 347、509、6 495个;其中,NAB1、JAK1、PIK3R1、TMOD1和S100A6等为共同上调的关键基因,而PROS1、GREB1、KLF9、CRABP2、GADD45B、Notch1、LATS2和SLFN11等为共同下调基因(差异>1.5倍;P均<0.05)。这些差异表达基因显著富集于表观遗传修饰、细胞周期调控、跨膜信号转导及化学排斥蛋白通道活性等分子功能,共同参与了细胞干性维持、细胞增殖调控、细胞分化程度降低及迁徙能力增高、细胞耐受及抗性增强等生物学进程,以及与卵巢癌发生、发展密切相关的ECM、ErbB和Hedgehog等信号通路。结论各卵巢癌干细胞中存在共有的干性差异表达基因、共同富集的生物学特性及特异信号调控网络。

Objective To analyze expression characteristics of ovarian cancer stem cells （OVCSCs） shared differentially expressed genes. Methods The genome-wide expression profiles from NCBI GEO database of cell lines and patients derived OVCSCs were integrated for comparative analysis towards their non-stemness counterparts. The shared OVCSC representing differentially expressed genes were identified by GeneSifter software, and mutual OVCSC biological characteristics and signaling pathways were conducted by enrichment analysis. Results Through analyzing OVC cell line IGROV1 and patients ascites derived side population cells （SPs） over non-SPs together with OVC cell line OVCAR-3 derived multiple cellular spheroid （MCS） over non-MCS, the number of differential expression genes was 1547, 509 and 6495 respectively, including shared key up-regulated genes NAB1, JAK1, PIK3R1, TMOD1 and S100A6, shared key down-regulated genes PROS1, GREB1, KLF9, CRABP2, GADD45B, Notchl, LATS2 and SLFN1 （fold change 〉 1.5, all P 〈0.05）. These differentially expressed genes were significantly enriched in molecular functions, such as epigenetic modifications, cell cycle regulation, transmembrane signal transduction and chemical repulsion protein channel activity ; they were involved in biological processes, such as stemness maintaining, regulation of cell proliferation, lowering cell differentiation degree, promoting migration ability, enhancing chemo-resistance and anti-apoptosis; and involved in signaling pathways such as ECM, ErbB and Hedgehog which were closely associated with OVC progression. Conclusion There were shared differentially expressed sternness genes, mutual enriched biological characteristics and regulation signaling pathways in various OVCSCs.