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

• Published in: British journal of cancer 2014-05, Vol.110 (10), p.2489-2495
• Main Authors: Azimi, A, Pernemalm, M, Frostvik Stolt, M, Hansson, J, Lehtiö, J, Egyházi Brage, S, Hertzman Johansson, C
• Format: Article
• Language: English
• Subjects: 631/45/475; 631/67/1059/2326; 631/67/1059/99; 631/67/1813/1634; Adult; Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biopsy; Cancer Research; Cancer therapies; Chemotherapy; Cystatin B - biosynthesis; Cystatin B - genetics; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Dacarbazine - therapeutic use; Dermatology; Drug Resistance; Drug Resistance, Neoplasm - physiology; Epidemiology; Factor XIII - biosynthesis; Factor XIII - genetics; Female; Gene expression; Gene Expression Profiling; Humans; Immunotherapy; Lymphatic Metastasis; Male; Mass spectrometry; Medical sciences; Medicin och hälsovetenskap; Melanoma; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - secondary; Melanoma, Cutaneous Malignant; Metastasis; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Myo-Inositol-1-Phosphate Synthase - biosynthesis; Myo-Inositol-1-Phosphate Synthase - genetics; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Neoplasm Proteins - physiology; Oncology; Prospective Studies; Proteins; Proteomics; Proteomics - methods; S100 Proteins - biosynthesis; S100 Proteins - genetics; S100 Proteins - physiology; Scientific imaging; Skin cancer; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Tandem Mass Spectrometry; Temozolomide; Translational Therapeutics; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Young Adult
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/bjc.2014.169

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.