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.
Oncol Rep. 2014 Jun;31(6):2601-10. doi: 10.3892/or.2014.3139. Epub 2014 Apr 16.
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.
纤连蛋白 4（fibulin-4）是细胞外糖蛋白纤连蛋白家族的成员之一，与多种类型癌症的进展有关。然而，纤连蛋白 4 在宫颈癌进展中的作用仍未被探索。通过实时逆转录-聚合酶链反应和免疫组织化学检测正常宫颈组织、宫颈上皮内瘤变（CIN）、宫颈癌、高侵袭性亚克隆和低侵袭性亚克隆中纤连蛋白 4 mRNA 和蛋白的表达水平。采用酶联免疫吸附试验检测 CIN 和宫颈癌患者的血清纤连蛋白 4 水平。为了评估纤连蛋白 4 的血管生成特性，通过免疫组织化学分析宫颈癌病例中血管内皮生长因子（VEGF）表达和肿瘤微血管密度（MVD）。纤连蛋白 4 在宫颈癌病例中表达上调，并与 MVD 和 VEGF 表达呈正相关。纤连蛋白 4 过表达和高血清水平与宫颈癌患者的晚期、低分化、淋巴结转移和预后不良显著相关。与低侵袭性亚克隆相比，纤连蛋白 4 在高侵袭性亚克隆中也表现出过度表达。纤连蛋白 4 是一种新鉴定的糖蛋白，在宫颈癌中过度表达。纤连蛋白 4 促进血管生成，并与不良的预后临床病理特征相关。本研究表明，纤连蛋白 4 可能作为宫颈癌的一个新的预后因素和潜在的治疗靶点。
