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过氧化物酶 2 和锌-α-2-糖蛋白作为潜在的联合新型唾液生物标志物,通过蛋白质组学方法用于早期检测口腔鳞状细胞癌。

Peroxiredoxin-2 and zinc-alpha-2-glycoprotein as potentially combined novel salivary biomarkers for early detection of oral squamous cell carcinoma using proteomic approaches.

机构信息

Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.

Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; HPV & EBV and Carcinogenesis Research Group, Khon Kaen University, Khon Kaen, Thailand.

出版信息

J Proteomics. 2018 Feb 20;173:52-61. doi: 10.1016/j.jprot.2017.11.022. Epub 2017 Dec 1.

Abstract

UNLABELLED

No effective screening method is available for oral squamous cell carcinoma (OSCC) that is recognized to influence by environmental factors as well as human papillomavirus (HPV) and Epstein-Barr virus (EBV). Therefore, we sought to identify salivary biomarkers for screening of OSCC with or without HPV and/or EBV infection. Saliva, lesion and oral exfoliated cells were collected from OSCC patients and cancer-free controls (CFCs) and grouped depending on their HPV- and EBV-infection status. Salivary protein was precipitated and subjected to 2-dimensional gel electrophoresis. Differential expression of proteins was identified by mass spectrometry and validated by Western blotting. Distinctive expression patterns of salivary proteins were detected in OSCC as compared with CFCs. Levels of peroxiredoxin-2 (PRDX-2) and zinc-alpha-2-glycoprotein (ZAG) were significantly up-regulated in OSCC cases (p<0.001) relative to CFCs. Similarly, these proteins were also up-regulated in lesion cells compared with oral exfoliated cells (p<0.001). However, the expression patterns of these proteins were not significantly influenced by patient histories (risk factors). In combination, these proteins yielded the highest discriminatory power (AUC=0.999), sensitivity (100%), and specificity (98.77%) in distinguishing the early stages of OSCC. The detection of PRDX-2 combining with ZAG protein could potentially be used as salivary biomarkers for early screening of OSCC.

SIGNIFICANCE

Our findings demonstrate a useful of combined detection of PRDX-2 and ZAG as a salivary biomarker for the early detection of OSCC.

摘要

未标记

口腔鳞状细胞癌(OSCC)目前尚无有效的筛查方法,该疾病被认为受环境因素、人乳头瘤病毒(HPV)和 Epstein-Barr 病毒(EBV)的影响。因此,我们试图确定用于筛查 HPV 和/或 EBV 感染的 OSCC 的唾液生物标志物。从 OSCC 患者和无癌症对照者(CFC)中收集唾液、病变和口腔脱落细胞,并根据 HPV 和 EBV 感染状态进行分组。沉淀唾液蛋白,进行二维凝胶电泳。通过质谱鉴定差异表达的蛋白质,并通过 Western blot 进行验证。与 CFC 相比,OSCC 患者的唾液蛋白表达模式存在明显差异。与 CFC 相比,过氧化物酶 2(PRDX-2)和锌-α-2-糖蛋白(ZAG)的水平在 OSCC 病例中显着上调(p<0.001)。同样,与口腔脱落细胞相比,这些蛋白质在病变细胞中也上调(p<0.001)。然而,这些蛋白质的表达模式不受患者病史(危险因素)的显著影响。这些蛋白质联合使用时,在区分 OSCC 的早期阶段时具有最高的辨别力(AUC=0.999)、灵敏度(100%)和特异性(98.77%)。PRDX-2 结合 ZAG 蛋白的检测可能可用于 OSCC 的早期唾液生物标志物检测。

意义

我们的研究结果表明,联合检测 PRDX-2 和 ZAG 作为 OSCC 早期检测的唾液生物标志物具有一定的应用价值。

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