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Fibulin-4 is associated with tumor progression and a poor prognosis in ovarian carcinomas.

Chen J, Liu Z, Fang S, Fang R, Liu X, Zhao Y, Li X, Huang L, Zhang J - BMC Cancer (2015)

Bottom Line: Fibulin-4 expression was upregulated in ovarian carcinoma, and positively correlated with MVD and VEGF expression.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, 250012, China. 77chenjie@sdu.edu.cn.

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.

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Related in: MedlinePlus

Fibulin-4 expressions in highly invasive subclones and low invasive subclones. (ABCD) Fibulin-4 protein expressions of highly invasive subclones S1 (A) and A1 (B) and low invasive subclones S21 (C) and A19 (D) as measured by ICC staining (Magnification × 200). (E) Fibulin-4 mRNA expressions of highly invasive subclones and low invasive subclones as measured by q-RT-PCR. (F) Fibulin-4 protein expressions of highly invasive subclones and low invasive subclones as measured by Western blot. *P < 0.05 versus control.
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Fig3: Fibulin-4 expressions in highly invasive subclones and low invasive subclones. (ABCD) Fibulin-4 protein expressions of highly invasive subclones S1 (A) and A1 (B) and low invasive subclones S21 (C) and A19 (D) as measured by ICC staining (Magnification × 200). (E) Fibulin-4 mRNA expressions of highly invasive subclones and low invasive subclones as measured by q-RT-PCR. (F) Fibulin-4 protein expressions of highly invasive subclones and low invasive subclones as measured by Western blot. *P < 0.05 versus control.

Mentions: The highly invasive subclone (S1 and A1) and the low invasive subclone (S21 and A19) were derived from the SKOV3 and 3AO human ovarian cancer cell lines, using the limited dilution method. Since the cell lines have had similar genetic backgrounds, they are suitable for comparative analysis. As shown in Figure 2B,C,D and Figure 3, the protein and mRNA expressions of fibulin-4 and VEGF were much higher in highly invasive subclones (S1 and A1), compared to the low invasive subclones (S21 and A19).Figure 3


Fibulin-4 is associated with tumor progression and a poor prognosis in ovarian carcinomas.

Chen J, Liu Z, Fang S, Fang R, Liu X, Zhao Y, Li X, Huang L, Zhang J - BMC Cancer (2015)

Fibulin-4 expressions in highly invasive subclones and low invasive subclones. (ABCD) Fibulin-4 protein expressions of highly invasive subclones S1 (A) and A1 (B) and low invasive subclones S21 (C) and A19 (D) as measured by ICC staining (Magnification × 200). (E) Fibulin-4 mRNA expressions of highly invasive subclones and low invasive subclones as measured by q-RT-PCR. (F) Fibulin-4 protein expressions of highly invasive subclones and low invasive subclones as measured by Western blot. *P < 0.05 versus control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4359517&req=5

Fig3: Fibulin-4 expressions in highly invasive subclones and low invasive subclones. (ABCD) Fibulin-4 protein expressions of highly invasive subclones S1 (A) and A1 (B) and low invasive subclones S21 (C) and A19 (D) as measured by ICC staining (Magnification × 200). (E) Fibulin-4 mRNA expressions of highly invasive subclones and low invasive subclones as measured by q-RT-PCR. (F) Fibulin-4 protein expressions of highly invasive subclones and low invasive subclones as measured by Western blot. *P < 0.05 versus control.
Mentions: The highly invasive subclone (S1 and A1) and the low invasive subclone (S21 and A19) were derived from the SKOV3 and 3AO human ovarian cancer cell lines, using the limited dilution method. Since the cell lines have had similar genetic backgrounds, they are suitable for comparative analysis. As shown in Figure 2B,C,D and Figure 3, the protein and mRNA expressions of fibulin-4 and VEGF were much higher in highly invasive subclones (S1 and A1), compared to the low invasive subclones (S21 and A19).Figure 3

Bottom Line: Fibulin-4 expression was upregulated in ovarian carcinoma, and positively correlated with MVD and VEGF expression.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, 250012, China. 77chenjie@sdu.edu.cn.

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.

Show MeSH
Related in: MedlinePlus