Efficacy of bortezomib in sarcomas with high levels of MAP17 (PDZK1IP1)
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Marco Perez1, Javier Peinado-Serrano1, Jose Manuel Garcia-Heredia1,2, Irene Felipe-Abrio1, Cristina Tous1, Irene Ferrer1, Javier Martin-Broto1,3, Carmen Saez1,4, Amancio Carnero1
1Instituto de Biomedicina de Sevilla, IBIS, Hospital Universitario Virgen del Rocio, Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Seville, Spain
2Department of Vegetal Biochemistry and Molecular Biology, University of Seville, Seville, Spain
3Department of Medical Oncology, Virgen del Rocío University Hospital, Seville, Spain
4Department of Pathology, Virgen del Rocío University Hospital, Seville, Spain
Amancio Carnero, email: [email protected]
Keywords: MAP17, bortezomib, PDX, sarcomas, biomarker
Received: March 08, 2016 Accepted: August 09, 2016 Published: August 22, 2016
Sarcomas are malignant tumors accounting for a high percentage of cancer morbidity and mortality in children and young adults. Surgery and radiation therapy are the accepted treatments for most sarcomas; however, patients with metastatic disease are treated with systemic chemotherapy. Many tumors display marginal levels of chemoresponsiveness, and new treatment approaches are needed. MAP17 is a small non-glycosylated membrane protein overexpressed in carcinomas. The levels of MAP17 could be used as a prognostic marker to predict the response to bortezomib in hematological malignancies and in breast tumors. Therefore, we analyzed the expression of this oncogene in sarcomas and its relationship with clinico-pathological features, as well as tested whether it can be used as a new biomarker to predict the therapeutic response to bortezomib and new therapies for sarcomas. We found that the levels of MAP17 were related to clinical features and poor survival in a cohort of 69 patients with different sarcoma types, not being restricted to any special subtype of tumor. MAP17 expression is associated with poor overall survival (p<0.001) and worse disease-free survival (p=0.002). Cell lines with high levels of MAP17 show a better response to bortezomib in vitro. Furthermore, patient-derived xenografts (PDX) with high levels of MAP17 respond to bortezomib in vivo. Our results showed that this response is due to the lower levels of NFκB and autophagy activation. Therefore, we suggest that MAP17 is a new biomarker to predict the efficacy of bortezomib as a new therapy for sarcomas.
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