title: Fibulin-4 is associated with tumor progression and a poor prognosis in ovarian carcinomas.
abstract: BACKGROUND
  Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progressions of some cancers. However, no information has been available to date regarding the function of fibulin-4 in ovarian carcinoma progression.
  
  
  METHODS
  In this study, fibulin-4 mRNA and protein expression in normal ovarian tissue, ovarian tumor, high invasive subclones and low invasive subclones were evaluated by immunohistochemistry and real time reverse transcriptase-polymerase chain reaction (RT-PCR). The serum levels of fibulin-4, cancer antigen 125 (CA-125) and cerbohydrate antigen 199 (CA19-9) in patients with ovarian tumor were measured by enzyme-linked immunosorbent assay and electrochemiluminescent immunoassay. To assess the angiogenic properties of fibulin-4, vascular endothelial growth factor (VEGF) expression and tumor microvessel density were analyzed in ovarian carcinoma by immunohistochemistry.
  
  
  RESULTS
  Fibulin-4 expression was upregulated in ovarian carcinoma, and positively correlated with MVD and VEGF expression. Fibulin-4 overexpression was significantly associated with advanced stage, low differentiation, lymph node metastasis and poor prognosis in patients with ovarian cancer. The serum levels of fibulin-4, CA-125 and CA19-9 in patients with ovarian carcinoma were much higher than those with benign ovarian tumors and normal controls. Compared to CA-125 and CA19-9, fibulin-4 had better diagnostic sensitivity and specificity.
  
  
  CONCLUSIONS
  Fibulin-4 is a novel gene that is found overexpressed in ovarian cancer and associated with poor prognostic clinicopathologic features. This study shows that fibulin-4 may serve as a new prognostic factor and as a potential therapeutic target for patients with ovarian cancer in the future.
authors.affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, 250012, China. 77chenjie@sdu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Hepatobiliary and Pancreatic Surgery, Jinan Central Hospital affiliated to Shandong University, Jinan, 250013, China. zxyyliuzhao@163.com.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Biochemistry & Molecular Biology, Georgetown University, Georgetown, Washington D.C, 20057, USA. sf647@georgetown.edu.
authors.forename: Shuang
authors.initials: S
authors.lastname: Fang
authors.affiliation: Grade 2011, Clinical Medicine, School of Medicine, Shandong University, Jinan, 250012, China. 408360528@qq.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Fang
authors.affiliation: Grade 2011, Clinical Medicine, School of Medicine, Shandong University, Jinan, 250012, China. liuxi2013liuxi@163.com.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, China. yrzhao@sdu.edu.cn.
authors.forename: Yueran
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Haematology, QiLu Hospital of Shandong University, Jinan, 250012, China. 18615656606@163.com.
authors.forename: XiangXin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, China. huangleichina@msn.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Central Laboratory, Shandong Provincial Hospital affiliated to Shandong University, Jinan, 250021, China. zhangjie19630711@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D018394:CA-125 Antigen / Q000097:blood; D045744:Cell Line, Tumor; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000098:blood supply* / Q000473:pathology; D011379:Prognosis; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C578959:carbohydrate antigen 199, human