Protein profiling of oral brush biopsies: S100A8 and S100A9 can differentiate between normal, premalignant, and tumor cells

Protein profiling of oral brush biopsies: S100A8 and S100A9 can differentiate between normal, premalignant, and tumor cells
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DOI:
10.1002/prca.200600669
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发表时间:
2007-05-01
影响因子:
2
通讯作者:
von Eggeling, Ferdinand
von Eggeling, Ferdinand
中科院分区:
生物学3区
文献类型:
--
作者:
Driemel, Oliver;Murzik, Ulrike;von Eggeling, Ferdinand

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在口腔粘膜病变中,通常很难区分前驱病变和已经表现出的口腔鳞状细胞癌。因此,多个手术刀活检是必要的,以检测肿瘤细胞已经在早期阶段,并保证准确的后续行动。我们分析了口腔刷活检(n = 49)的正常粘膜,炎症和过度增生性病变,口腔鳞状细胞癌与蛋白质芯片阵列(SELDI)作为一种非侵入性的方法来表征假定的肿瘤细胞。发现三种蛋白质在这三个阶段之间存在差异。这三种蛋白能够以100%的灵敏度和91%的特异性区分正常细胞和肿瘤细胞,并且可以以高达91%的灵敏度和高达90%的特异性区分炎性/过度增殖性病变和肿瘤细胞。这些蛋白质中的两个已经通过免疫耗竭鉴定为S100 A8和S100 A9,并且该鉴定通过免疫细胞化学证实。刷检首次成功用于蛋白质组生物标志物的发现。所鉴定的蛋白质标志物对于区分所分析的三个阶段具有高度特异性,并由此反映从正常到癌前非发育异常并最终到肿瘤组织的进展。这一知识可作为监测粘膜病变的第一诊断步骤。
In oral mucosa lesions it is frequently difficult to differentiate between precursor lesions and already manifest oral squamous cell carcinoma. Therefore, multiple scalpel biopsies are necessary to detect tumor cells already in early stages and to guarantee an accurate follow-up. We analyzed oral brush biopsies (n = 49) of normal mucosa, inflammatory and hyperproliferative lesions, and oral squamous cell carcinoma with ProteinChip Arrays (SELDI) as a non-invasive method to characterize putative tumor cells. Three proteins were found that differentiated between these three stages. These three proteins are able to distinguish between normal cells and tumor cells with a sensitivity of 100% and specificity of 91% and can distinguish inflammatory/ hyperproliferative lesions from tumor cells with a sensitivity of up to 91% and specificity of up to 90%. Two of these proteins have been identified by immunodepletion as S100A8 and S100A9 and this identification was confirmed by immunocytochemistry. For the first time, brush biopsies have been successfully used for proteomic biomarker discovery. The identified protein markers are highly specific for the distinction of the three analyzed stages and therewith reflect the progression from normal to premalignant non-dysplastic and finally to tumor tissue. This knowledge could be used as a first diagnostic step in the monitoring of mucosal lesions.