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鉴定人类口腔鳞状细胞癌患者血清中的宿主免疫反应蛋白候选物。

Identification of host-immune response protein candidates in the sera of human oral squamous cell carcinoma patients.

作者信息

Chen Yeng, Azman Siti Nuraishah, Kerishnan Jesinda P, Zain Rosnah Binti, Chen Yu Nieng, Wong Yin-Ling, Gopinath Subash C B

机构信息

Department of Oral Biology & Biomedical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research and Coordinating Center, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.

Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Georgetown, Penang, Malaysia.

出版信息

PLoS One. 2014 Oct 1;9(10):e109012. doi: 10.1371/journal.pone.0109012. eCollection 2014.

Abstract

One of the most common cancers worldwide is oral squamous cell carcinoma (OSCC), which is associated with a significant death rate and has been linked to several risk factors. Notably, failure to detect these neoplasms at an early stage represents a fundamental barrier to improving the survival and quality of life of OSCC patients. In the present study, serum samples from OSCC patients (n = 25) and healthy controls (n = 25) were subjected to two-dimensional gel electrophoresis (2-DE) and silver staining in order to identify biomarkers that might allow early diagnosis. In this regard, 2-DE spots corresponding to various up- and down-regulated proteins were sequenced via high-resolution MALDI-TOF mass spectrometry and analyzed using the MASCOT database. We identified the following differentially expressed host-specific proteins within sera from OSCC patients: leucine-rich α2-glycoprotein (LRG), alpha-1-B-glycoprotein (ABG), clusterin (CLU), PRO2044, haptoglobin (HAP), complement C3c (C3), proapolipoprotein A1 (proapo-A1), and retinol-binding protein 4 precursor (RBP4). Moreover, five non-host factors were detected, including bacterial antigens from Acinetobacter lwoffii, Burkholderia multivorans, Myxococcus xanthus, Laribacter hongkongensis, and Streptococcus salivarius. Subsequently, we analyzed the immunogenicity of these proteins using pooled sera from OSCC patients. In this regard, five of these candidate biomarkers were found to be immunoreactive: CLU, HAP, C3, proapo-A1 and RBP4. Taken together, our immunoproteomics approach has identified various serum biomarkers that could facilitate the development of early diagnostic tools for OSCC.

摘要

口腔鳞状细胞癌(OSCC)是全球最常见的癌症之一,其死亡率很高,且与多种风险因素有关。值得注意的是,未能在早期阶段检测出这些肿瘤是提高OSCC患者生存率和生活质量的一个基本障碍。在本研究中,对OSCC患者(n = 25)和健康对照者(n = 25)的血清样本进行二维凝胶电泳(2-DE)和银染,以鉴定可能有助于早期诊断的生物标志物。在这方面,通过高分辨率基质辅助激光解吸电离飞行时间质谱对与各种上调和下调蛋白相对应的2-DE斑点进行测序,并使用MASCOT数据库进行分析。我们在OSCC患者的血清中鉴定出以下差异表达的宿主特异性蛋白:富含亮氨酸的α2-糖蛋白(LRG)、α-1-B-糖蛋白(ABG)、簇集蛋白(CLU)、PRO2044、触珠蛋白(HAP)、补体C3c(C3)、前载脂蛋白A1(proapo-A1)和视黄醇结合蛋白4前体(RBP4)。此外,还检测到五种非宿主因子,包括来自沃氏不动杆菌、多食伯克霍尔德菌、黄色粘球菌、香港拉氏菌和唾液链球菌的细菌抗原。随后,我们使用OSCC患者的混合血清分析了这些蛋白的免疫原性。在这方面,发现这些候选生物标志物中有五种具有免疫反应性:CLU、HAP、C3、proapo-A1和RBP4。综上所述,我们的免疫蛋白质组学方法已经鉴定出多种血清生物标志物,这些生物标志物有助于开发OSCC的早期诊断工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/14a4/4182798/5d69bd227580/pone.0109012.g001.jpg

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