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S100-A10, thioredoxin, and S100-A6 as biomarkers of papillary thyroid carcinoma with lymph node metastasis identified by MALDI Imaging.

J. Mol. Med. 90, 163-174 (2012)
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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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 < 0.005). For functional analysis of the metastasis-specific proteins, we performed an Ingenuity Pathway Analysis and discovered a strong relationship of all candidates with the TGF-β-dependent EMT pathway. Our results demonstrated the potential application of the MALDI-IMS proteomic approach in identifying protein markers of metastasis in PTC. The novel protein markers identified in this study may be used for risk stratification regarding metastatic potential in PTC.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter S100-A10; S100-A6; Thioredoxin; MALDI imaging; Papillary thyroid cancer; Metastasis
ISSN (print) / ISBN 0946-2716
e-ISSN 1432-1440
Zeitschrift Journal of Molecular Medicine
Quellenangaben Band: 90, Heft: 2, Seiten: 163-174 Artikelnummer: , Supplement: ,
Verlag Springer