title: Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies.
abstract: OBJECTIVE
  To understand the chemotherapy response program in ovarian cancer cells at deep transcript sequencing levels.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Our database offers the first comprehensive view of the digital transcriptomes of ovarian cancer cell lines and tissues with different chemotherapy response phenotypes.
authors.affiliation: Systems Biology Division, Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou 310029, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Cheng
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Bhushan
authors.initials: B
authors.lastname: Kulkarni
authors.forename: Tanja
authors.initials: T
authors.lastname: Pejovic
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yan
authors.forename: Jung-Hsien
authors.initials: JH
authors.lastname: Chiang
authors.forename: Leroy
authors.initials: L
authors.lastname: Hood
authors.forename: Kunle
authors.initials: K
authors.lastname: Odunsi
authors.forename: Biaoyang
authors.initials: B
authors.lastname: Lin
mesh_terms: D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D016190:Carboplatin; D002945:Cisplatin