title: ZNF385B and VEGFA are strongly differentially expressed in serous ovarian carcinomas and correlate with survival.
abstract: BACKGROUND
  The oncogenesis of ovarian cancer is poorly understood. The aim of this study was to identify mRNAs differentially expressed between moderately and poorly differentiated (MD/PD) serous ovarian carcinomas (SC), serous ovarian borderline tumours (SBOT) and superficial scrapings from normal ovaries (SNO), and to correlate these mRNAs with clinical parameters including survival.
  
  
  METHODS
  Differences in mRNA expression between MD/PD SC, SBOT and SNO were analyzed by global gene expression profiling (n = 23), validated by RT-qPCR (n = 41) and correlated with clinical parameters.
  
  
  RESULTS
  Thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected from the global gene expression analyses, and 21 were verified (p<0.01) by RT-qPCR. Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. ZNF385B was downregulated (FC = -130.5, p = 1.2×10(-7)) and correlated with overall survival (p = 0.03). VEGFA was upregulated (FC = 6.1, p = 6.0×10(-6)) and correlated with progression-free survival (p = 0.037). Increased levels of TPX2 and FOXM1 mRNAs (FC = 28.5, p = 2.7×10(-10) and FC = 46.2, p = 5.6×10(-4), respectively) correlated with normalization of CA125 (p = 0.03 and p = 0.044, respectively). Furthermore, we present a molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and directly interacting with TP53.
  
  
  CONCLUSIONS
  We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including ZNF385B and VEGFA correlating with survival, and FOXM1 and TPX2 with normalization of CA125. We also present a molecular pathway for MD/PD SC.
authors.affiliation: Department of Gynaecological Oncology, Oslo University Hospital, Oslo, Norway. bente.vilming.elgaaen@medisin.uio.no
authors.forename: Bente Vilming
authors.initials: BV
authors.lastname: Elgaaen
authors.forename: Ole Kristoffer
authors.initials: OK
authors.lastname: Olstad
authors.forename: Leiv
authors.initials: L
authors.lastname: Sandvik
authors.forename: Elin
authors.initials: E
authors.lastname: Odegaard
authors.forename: Torill
authors.initials: T
authors.lastname: Sauer
authors.forename: Anne Cathrine
authors.initials: AC
authors.lastname: Staff
authors.forename: Kaare M
authors.initials: KM
authors.lastname: Gautvik
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C494418:ZNF385A protein, human