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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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Receiver operator characteristic(ROC)curves of fibulin-4,CA-125 and CA19-9 in patients with ovarian cancer. The area under the curve (AUC) of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting their clinical usefulness for diagnosing ovarian carcinoma was moderate.
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Fig4: Receiver operator characteristic(ROC)curves of fibulin-4,CA-125 and CA19-9 in patients with ovarian cancer. The area under the curve (AUC) of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting their clinical usefulness for diagnosing ovarian carcinoma was moderate.

Mentions: As shown in Table 4, the serum levels of fibulin-4, CA-125 and CA19-9 in patients with ovarian carcinoma was much higher than that with benign ovarian tumor and healthy controls (P < 0.05). No significant difference was found between healthy control and benign ovarian tumor (P >0.05). Moreover, high serum levels of fibulin-4, CA-125 and CA19-9 were associated with low differentiation, advanced stage and positive lymph node status of ovarian carcinomas (P < 0.05). There were no significant differences in the serum levels of fibulin-4 among different pathology types of ovarian carcinoma (P >0.05). However, the serum level of CA-125 was increased in serous cystadenocarcinoma and CA19-9 was increased in mucinous cystadenocarcinoma (P < 0.05). The serum levels of fibulin-4, CA-125 and CA19-9 were evaluated by ROC analysis (Figure 4). The AUC of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting that clinical usefulness of the three biomarkers for diagnosing ovarian carcinoma was moderate. The Youden index [42] identified the cut-off level of fibulin-4 was 45.79 ng/ml, with a sensitivity of 75.0% and a specificity of 84.0%. Table 5 shows the comparisons of sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio among the three markers. In combined measurements, when 2 markers were both determined in diagnosis of ovarian cancer, combination of fibulin-4 and CA-125 was superior to other two combinations. When combined fibulin-4, CA-125 and CA19-9, the diagnostic specificity, positive predictive value and positive likelihood ratio were all significantly increased.Table 4


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)

Receiver operator characteristic(ROC)curves of fibulin-4,CA-125 and CA19-9 in patients with ovarian cancer. The area under the curve (AUC) of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting their clinical usefulness for diagnosing ovarian carcinoma was moderate.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig4: Receiver operator characteristic(ROC)curves of fibulin-4,CA-125 and CA19-9 in patients with ovarian cancer. The area under the curve (AUC) of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting their clinical usefulness for diagnosing ovarian carcinoma was moderate.
Mentions: As shown in Table 4, the serum levels of fibulin-4, CA-125 and CA19-9 in patients with ovarian carcinoma was much higher than that with benign ovarian tumor and healthy controls (P < 0.05). No significant difference was found between healthy control and benign ovarian tumor (P >0.05). Moreover, high serum levels of fibulin-4, CA-125 and CA19-9 were associated with low differentiation, advanced stage and positive lymph node status of ovarian carcinomas (P < 0.05). There were no significant differences in the serum levels of fibulin-4 among different pathology types of ovarian carcinoma (P >0.05). However, the serum level of CA-125 was increased in serous cystadenocarcinoma and CA19-9 was increased in mucinous cystadenocarcinoma (P < 0.05). The serum levels of fibulin-4, CA-125 and CA19-9 were evaluated by ROC analysis (Figure 4). The AUC of fibulin-4, CA-125 and CA19-9 were 0.883, 0.808 and 0.701, suggesting that clinical usefulness of the three biomarkers for diagnosing ovarian carcinoma was moderate. The Youden index [42] identified the cut-off level of fibulin-4 was 45.79 ng/ml, with a sensitivity of 75.0% and a specificity of 84.0%. Table 5 shows the comparisons of sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio among the three markers. In combined measurements, when 2 markers were both determined in diagnosis of ovarian cancer, combination of fibulin-4 and CA-125 was superior to other two combinations. When combined fibulin-4, CA-125 and CA19-9, the diagnostic specificity, positive predictive value and positive likelihood ratio were all significantly increased.Table 4

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