S100-A10, thioredoxin, and S100-A6 as biomarkers of papillary thyroid carcinoma with lymph node metastasis identified by MALDI Imaging
S100-A10, thioredoxin, and S100-A6 as biomarkers of papillary thyroid carcinoma with lymph node metastasis identified by MALDI Imaging
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DOI：
10.1007/s00109-011-0815-6
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发表时间：
2012-02-01
影响因子：
4.7
通讯作者：
Zitzelsberger, Horst
中科院分区：
文献类型：
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作者：
Nipp, Martin;Elsner, Mareike;Zitzelsberger, Horst
在甲状腺乳头状癌（PTC）中，转移是侵袭性肿瘤表型的一个特征。为了确定区分患者侵袭性肿瘤行为的蛋白质生物标志物，对转移性和非转移性肿瘤的蛋白质组学特征进行了比较研究。特别是，基质辅助激光解吸/电离（MALDI）成像质谱（IMS）被用于分析原发肿瘤样本。我们调查了一组年龄、肿瘤分期和性别匹配的PTC肿瘤队列（n=118）。对发现组（n=29）进行MALDI-IMS蛋白质组学筛选。鉴别质量峰相关蛋白通过1d凝胶电泳和质谱鉴定。候选蛋白随后使用独立PTC验证集（n=89）的组织微阵列进行免疫组织化学（IHC）验证。在本研究中，我们发现36个质量电荷比（m/z）特异区分转移性和非转移性肿瘤的物种，其中m/z 11,608鉴定为硫氧还蛋白，m/z 11,184鉴定为S100-A10， m/z 10,094鉴定为S100-A6。此外，在验证集上使用免疫组化，我们发现这三种蛋白的过表达与PTC的淋巴结转移高度相关(p
In papillary thyroid carcinoma (PTC), metastasis is a feature of an aggressive tumor phenotype. To identify protein biomarkers that distinguish patients with an aggressive tumor behavior, proteomic signatures in metastatic and non-metastatic tumors were investigated comparatively. In particular, matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) was used to analyze primary tumor samples. We investigated a tumor cohort of PTC (n=118) that were matched for age, tumor stage, and gender. Proteomic screening by MALDI-IMS was performed for a discovery set (n=29). Proteins related to the discriminating mass peaks were identified by 1D-gel electrophoresis followed by mass spectrometry. The candidate proteins were subsequently validated by immunohistochemistry (IHC) using a tissue microarray for an independent PTC validation set (n=89). In this study, we found 36 mass-to-charge-ratio (m/z) species that specifically distinguished metastatic from non-metastatic tumors, among which m/z 11,608 was identified as thioredoxin, m/z 11,184 as S100-A10, and m/z 10,094 as S100-A6. Furthermore, using IHC on the validation set, we showed that the overexpression of these three proteins was highly associated with lymph node metastasis in PTC (p