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

Abstract

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.

• Authors: Martin Nipp, Mareike Elsner, Benjamin Balluff, Stephan Meding, Hakan Sarioglu, Marius Ueffing, Sandra Rauser, Kristian Unger, Heinz Höfler, Axel Walch, Horst Zitzelsberger
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 90 Issue 2 Pg. 163-74 (Feb 2012) ISSN: 1432-1440 [Electronic] Germany
• PMID: 21938494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• S100 Proteins
• Thioredoxins

Topics

• Adult
• Biomarkers, Tumor (genetics, metabolism)
• Carcinoma
• Carcinoma, Papillary
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lymph Nodes (metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• S100 Proteins (genetics, metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Thioredoxins (genetics, metabolism)
• Thyroid Cancer, Papillary
• Thyroid Neoplasms (diagnosis, metabolism, pathology)