Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou 310029, China.
Gynecol Oncol. 2010 May;117(2):159-69. doi: 10.1016/j.ygyno.2010.01.041. Epub 2010 Feb 23.
To understand the chemotherapy response program in ovarian cancer cells at deep transcript sequencing levels.
Two next-generation sequencing technologies--MPSS (massively parallel signature sequencing) and SBS (sequencing by synthesis)--were used to sequence the transcripts of IGROV1 and IGROV1-CP cells, and to sequence the transcripts of a highly chemotherapy responsive and a highly chemotherapy resistant ovarian cancer tissue.
We identified 3422 signatures (2957 genes) that are significantly different between IGROV1 and IGROV1-CP cells (P<0.001). Gene Ontology (GO) term GO:0001837 (epithelial-to-mesenchymal transition) and GO:0034330 (cell junction assembly and maintenance) are enriched in genes that are over expressed in IGROV1-CP cells while apoptosis-related GO terms are enriched in genes over expressed in IGROV1 cells. We identified 1187 tags (corresponding to 1040 genes) that are differentially expressed between the chemotherapy responsive and the persistently chemotherapy resistant ovarian cancer tissues. GO term GO:0050673 (epithelial cell proliferation) and GO:0050678 (regulation of epithelial cell proliferation) are enriched in the genes over expressed in the chemotherapy resistant tissue while the GO:0007229 (integrin-mediated signaling pathway) is enriched in the genes over expressed in the chemotherapy sensitive tissue. An integrative analysis identified 111 common differentially expressed genes including two bone morphogenetic proteins (BMP4 and BMP7), six solute carrier proteins (SLC10A3, SLC16A3, SLC25A1, SLC35B3, SLC7A5 and SLC7A7), transcription factor POU5F1 (POU class 5 homeobox 1), and KLK10 (kallikrein-related peptidase 10). A network analysis revealed a subnetwork with three genes BMP7, NR2F2 and AP2B1 that were consistently over expressed in the chemoresistant tissue or cells compared to the chemosensitive tissue or cells.
Our database offers the first comprehensive view of the digital transcriptomes of ovarian cancer cell lines and tissues with different chemotherapy response phenotypes.
在深度转录组测序水平上了解卵巢癌细胞的化疗反应程序。
使用两种下一代测序技术——MPSS（大规模平行签名测序）和 SBS（合成测序）——对 IGROV1 和 IGROV1-CP 细胞的转录本进行测序，并对高度化疗敏感和高度化疗耐药的卵巢癌组织的转录本进行测序。
我们鉴定了 3422 个标记物（2957 个基因），它们在 IGROV1 和 IGROV1-CP 细胞之间存在显著差异（P<0.001）。GO 术语 GO:0001837（上皮-间充质转化）和 GO:0034330（细胞连接组装和维持）在 IGROV1-CP 细胞中过度表达的基因中富集，而与凋亡相关的 GO 术语在 IGROV1 细胞中过度表达的基因中富集。我们鉴定了 1187 个标记物（对应于 1040 个基因），它们在化疗敏感和持续化疗耐药的卵巢癌组织之间存在差异表达。GO 术语 GO:0050673（上皮细胞增殖）和 GO:0050678（调节上皮细胞增殖）在化疗耐药组织中过度表达的基因中富集，而 GO:0007229（整合素介导的信号通路）在化疗敏感组织中过度表达的基因中富集。综合分析确定了 111 个共同差异表达的基因，包括两个骨形态发生蛋白（BMP4 和 BMP7）、六个溶质载体蛋白（SLC10A3、SLC16A3、SLC25A1、SLC35B3、SLC7A5 和 SLC7A7）、转录因子 POU5F1（POU 类 5 同源框 1）和 KLK10（激肽释放酶相关肽 10）。网络分析揭示了一个包含三个基因 BMP7、NR2F2 和 AP2B1 的子网络，这些基因在耐药组织或细胞中比在敏感组织或细胞中一致过度表达。
我们的数据库提供了卵巢癌细胞系和具有不同化疗反应表型的组织的数字转录组的第一个全面视图。
