Abstract
BackgroundFibulin-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.MethodsIn 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.ResultsFibulin-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.ConclusionsFibulin-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.
Highlights
Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progressions of some cancers
In most ovarian carcinomas, fibulin-4 immunoreactivity was high, and high fibulin-4 protein expression was found in the cytoplasm of ovarian cancer cells (Figure 1E,F,G)
High fibulin-4 protein expression was associated with low differentiation, advanced stage and positive lymph node status of Western blot Cells were lysed by using RIPA buffer containing 1 mM PMSF
Summary
Fibulin-4, a member of the fibulin family of extracellular glycoproteins, is implicated in the progressions of some cancers. Fibulin-2 [9,10] and fibulin-5 [11,12,13] were widely considered to be associated with the suppression of tumor growth, invasion, and angiogenesis. Few researchers reported oncogenic activities [14,15,16,17,18,19,20], whereas others have reported tumorsuppressive activities [21,22,23,24,25,26,27,28] This discrepancy may be attributable to the influence of the tumor microenvironment on tumor-associated genes in promoting angiogenesis and metastasis [29]
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