title: Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma.
abstract: Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progression of a number of types of cancer. However, the function of fibulin-4 in cervical cancer progression remains unexplored. Fibulin-4 mRNA and protein expression levels in normal cervical tissue, cervical intraepithelial neoplasia (CIN), cervical carcinoma, highly invasive subclones and low-invasive subclones were evaluated by real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. Serum fibulin-4 levels in patients with CIN and cervical carcinoma were measured by enzyme-linked immunosorbent assay. To assess the angiogenic properties of fibulin-4, vascular endothelial growth factor (VEGF) expression and tumor microvessel density (MVD) were analyzed in the cervical carcinoma cases by immunohistochemistry. Fibulin-4 expression was upregulated in the cervical carcinoma cases, and was positively correlated with MVD and VEGF expression. Fibulin-4 overexpression and high serum levels were significantly associated with advanced stage, low differentiation, lymph node metastasis, and poor prognosis in patients with cervical cancer. Fibulin-4 expression was also found to be overexpressed in highly invasive subclones when compared with the low-invasive subclones. Fibulin-4 is a newly identified glycoprotein that is overexpressed in cervical carcinoma. Fibulin-4 promotes angiogenesis and is associated with poor prognostic clinicopathologic features. This study demonstrated that fibulin-4 may serve as a new prognostic factor and as a potential therapeutic target for patients with cervical carcinoma.
authors.affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Fang
authors.affiliation: Central Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Yueran
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors.forename: Demei
authors.initials: D
authors.lastname: Ma
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D002277:Carcinoma / Q000097:blood* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C403672:EFEMP2 protein, human; D016326:Extracellular Matrix Proteins