Related Experiment Video
Updated: May 1, 2026
A Robust Discovery Platform for the Identification of Novel Mediators of Melanoma Metastasis
Published on: March 8, 2022
Proteomics analysis of melanoma metastases: association between S100A13 expression and chemotherapy resistance
A Azimi1, M Pernemalm2, M Frostvik Stolt1
1Department of Oncology-Pathology, Karolinska Institutet, CCK R8:03, Karolinska University Hospital, Solna, S-17176 Stockholm, Sweden.
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.
Insights
This study identified S100A13 as a protein overexpressed in non-responders to dacarbazine (DTIC) or temozolomide (TMZ) chemotherapy for cutaneous malignant melanoma (CMM). This suggests S100A13 may predict resistance to these melanoma treatments.
Area of Science:
- Oncology
- Proteomics
- Biochemistry
Background:
- Disseminated cutaneous malignant melanoma (CMM) often shows resistance to standard chemotherapy.
- Predictive markers for therapy response in CMM are currently lacking.
Purpose of the Study:
- To identify proteins impacting treatment response in CMM patients.
- To investigate potential biomarkers for dacarbazine (DTIC) or temozolomide (TMZ) chemotherapy resistance.
Main Methods:
- Proteomic profiling of lymph node metastasis samples from CMM patients using tandem mass spectrometry.
- Comparison of proteome differences between chemotherapy responders and non-responders.
- Validation of differentially expressed proteins (S100A13, CSTB) using immunoblotting and immunohistochemistry.
Main Results:
- Proteomic analysis revealed differences in signaling pathways, including Rho signaling, between responders and non-responders.
- The calcium-binding protein S100A13 was significantly overexpressed in non-responders compared to responders.
- S100A13 overexpression was consistently observed across multiple validation analyses.
Conclusions:
- S100A13 is implicated in CMM resistance to DTIC/TMZ chemotherapy.
- S100A13 represents a potential predictive biomarker for treatment response in CMM.
