Gelsolin and Ceruloplasmin as Potential Predictive Biomarkers for Cervical Cancer by 2D-DIGE Proteomics Analysis
Gelsolin and Ceruloplasmin as Potential Predictive Biomarkers for Cervical Cancer by 2D-DIGE Proteomics Analysis
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DOI：
10.1007/s12253-013-9670-9
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发表时间：
2014-01-01
影响因子：
2.8
通讯作者：
Jamal, Rahman
中科院分区：
文献类型：
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作者：
Lokamani, Ilambarthi;Looi, Mee-Lee;Jamal, Rahman
本研究旨在利用2D-DGE技术筛选出可作为宫颈癌潜在生物学标志物的候选蛋白质。对正常对照组、宫颈上皮内瘤变3级(CIN 3)、早期鳞癌(SCC I、II)和晚期(SCC III、IV)患者的血清标本进行2D-DGE检测。串联质谱仪鉴定差异表达斑点。然后分别用ELISA法和免疫组织化学法(IHC)验证血清和组织样本中的候选蛋白。共鉴定出20个差异表达蛋白。这些蛋白在细胞凋亡途径、补体系统、激素、脂肪酸、脂肪、维生素E和药物转运、凝血级联、铁调节和免疫反应等多种运输途径中发挥关键作用。根据它们与各种癌症进展的功能相关性，选择了4种蛋白质，即补体因子H、CD5样抗原、明胶蛋白和铜蓝蛋白，用于进一步的ELISA法验证。生物网络分析表明，铜蓝蛋白和明胶蛋白与癌基因NF-kappa b相互作用紧密，并通过免疫组化进一步验证了这两种蛋白的活性。明胶蛋白和铜蓝蛋白可作为高度恶性病变进展的潜在预测生物标志物。
This study aimed to identify candidate proteins which may serve as potential biological markers for cervical cancer using 2D-DIGE. Serum samples of controls, patients with cervical intraepithelial neoplasia grade 3 (CIN 3), squamous cell carcinoma of early (SCC I and II) and late (SCC III and IV) stage were subjected to 2D-DIGE. Differentially expressed spots were identified by tandem mass spectrometry. Validation of candidate proteins in serum and tissue samples were then performed by ELISA and immunohistochemistry (IHC) analysis respectively. A total of 20 differentially expressed proteins were identified. These proteins were found to play key roles in the apoptosis pathway, complement system, various types of transportation such as hormones, fatty acids, lipid, vitamin E and drug transportation, coagulation cascade, regulation of iron and immunologic response. Based on their functional relevancy to the progression of various cancers, 4 proteins namely the complement factor H, CD5-like antigen, gelsolin and ceruloplasmin were chosen for further validation using ELISA. Biological network analysis showed that ceruloplasmin and gelsolin are closely interacted with the oncogene NF-kappa b. These two proteins were further validated using the IHC. Gelsolin and ceruloplasmin may serve as potential predictive biomarkers for the progression of high grade lesions.