Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

Chen,Jie; Zhang,Jie; Liu,Xi; Fang,Rui; Zhao,Yueran; Ma,Demei

doi:10.3892/or.2014.3139

Overexpression of fibulin-4 is associated with tumor progression and poor prognosis in patients with cervical carcinoma

Authors:
- Jie Chen
- Jie Zhang
- Xi Liu
- Rui Fang
- Yueran Zhao
- Demei Ma
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Affiliations: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, Shandong 250012, P.R. China, Central Laboratory, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Obstetrics and Gynecology, Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: April 16, 2014 https://doi.org/10.3892/or.2014.3139
Pages: 2601-2610

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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.

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