Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance - PubMed (original) (raw)

Comparative Study

. 2014 May 13;110(10):2489-95.

doi: 10.1038/bjc.2014.169. Epub 2014 Apr 10.

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Comparative Study

Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance

A Azimi et al. Br J Cancer. 2014.

Abstract

Background: Disseminated cutaneous malignant melanoma (CMM) is commonly unresponsive to standard chemotherapies, and there are as yet no predictive markers of therapy response.

Methods: In the present study we collected fresh-frozen pretreatment lymph-node metastasis samples (n=14) from melanoma patients with differential response to dacarbazine (DTIC) or temozolomide (TMZ) chemotherapy, to identify proteins with an impact on treatment response. We performed quantitative protein profiling using tandem mass spectrometry and compared the proteome differences between responders (R) and non-responders (NR), matched for age, gender and histopathological type of CMM.

Results: Biological pathway analyses showed several signalling pathways differing between R vs NR, including Rho signalling. Gene expression profiling data was available for a subset of the samples, and the results were compared with the proteomics data. Four proteins with differential expression between R and NR were selected for technical validation by immunoblotting (ISYNA1, F13A1, CSTB and S100A13), and CSTB and S100A13 were further validated on a larger sample set by immunohistochemistry (n=48). The calcium binding protein S100A13 was found to be significantly overexpressed in NR compared with R in all analyses performed.

Conclusions: Our results suggest that S100A13 is involved in CMM resistance to DTIC/TMZ.

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Figures

Figure 1

Figure 1

Immunoblot results. (A) Comparison of proteomics and immunobloting results. Data are shown as the log2 of the mean of the fold change in responders over the value in non-responders. (B–D) Immunoblot images for four candidate proteins.

Figure 2

Figure 2

Immunohistochemistry. Representative images of metastases from DTIC/TMZ responders and non-responders, stained with antibodies for S100A13, CSTB or negative control without any primary antibody.

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