S100A8 as potential salivary biomarker of oral squamous cell carcinoma using nanoLC-MS/MS

S100A8 as potential salivary biomarker of oral squamous cell carcinoma using nanoLC-MS/MS
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DOI:
10.1016/j.cca.2014.05.009
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发表时间:
2014-09-25
影响因子:
5
通讯作者:
Lin, Cheng-Wen
Lin, Cheng-Wen
中科院分区:
医学3区
文献类型:
--
作者:
Jou, Yu-Jen;Hua, Chun-Hung;Lin, Cheng-Wen

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背景:口腔鳞状细胞癌(OSCC)的5年生存率较低,早期治疗可大大降低死亡率和发病率。唾液是一种非侵入性的样本,具有发现早期检测生物标志物的良好潜力。方法:利用NanoLC-MS/MS分析了35例正常对照和29例口腔鳞癌患者T1期、T2期、14例和T4期患者的唾液蛋白质组。结果:对10~15 kDa唾液蛋白进行NanoLC-MS/MS分析,在T3和T4期口腔鳞癌中鉴定出S100A8、Hb Delta和γ-G珠蛋白,在T1和T2期口腔鳞癌中鉴定出S100A7。免疫印迹和酶联免疫吸附试验显示唾液S100A8的增加与肿瘤大小、分期呈正相关。口腔鳞癌T1、T2、T3、T4期患者唾液中S100A8水平分别为3.4%、13.9%、92.9%和100%。唾液S100A7在T1和T2患者中分别占20.7%和11.1%。AUROC曲线显示基于S100A8的EL ISA检测口腔鳞癌具有较高的灵敏度、特异性和准确性。结论:纳米LC-MS/MS、Western印迹和ELISA法均表明唾液S100A8是检测口腔鳞癌患者的一种特异、敏感的标志物。唾液S100A8蛋白可用于口腔鳞癌的诊断。(C)2014爱思唯尔B.V.保留所有权利。
Background: Oral squamous cell carcinoma (OSCC) shows low 5-year survival; early treatment greatly reduces mortality and morbidity. Saliva is a non-invasive sample, with good potential to discover biomarkers for early detection.Methods: NanoLC-MS/MS served to analyze saliva proteome from control subjects (n = 35) and OSCC patients T1 (n = 29), T2 (n = 36), T3 (n = 14) and T4 (n = 21) stages. Identified biomarkers were verified by Western blot and ELISA assays.Results: NanoLC-MS/MS analysis of salivary proteins between 10 and 15 kDa identified S100A8, hemoglobin delta and gamma-G globin in T3 and T4 stage OSCC as well as S100A7 in T1 and T2 stage OSCC. Western blot and ELISA indicated positive correlation between salivary S100A8 increment and tumor size stage. High level of S100A8 appeared in 3.4, 13.9, 92.9, and 100% of saliva OSCC patients with T1, T2, T3, and T4 stages, respectively. Significant increase of salivary S100A7 was observed in 20.7% and 11.1% of those with T1 and T2, respectively. AUROC curve indicated high sensitivity, specificity and accuracy of S100A8-based ELISA as a detector.Conclusions: NanoLC-MS/MS, Western blot and ELISA manifested salivary S100A8 as a specific and sensitive marker for detection of OSCC patients. Salivary S100A8 protein could be applicable in developing OSCC diagnostics. (C) 2014 Elsevier B.V. All rights reserved.