Up-regulation of SERPINA3 correlates with high mortality of melanoma patients and increased migration and invasion of cancer cells

// Jiaying Zhou 1, * , Yabin Cheng 2, 3, * , Liren Tang 4 , Magdalena Martinka 5 , Sunil Kalia 3 1 Faculty of Science, University of British Columbia, Vancouver, BC, Canada 2 School of Pharmaceutical Sciences, Xiamen University, Xiamen, China 3 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada 4 Welichem Biotech Inc, Burnaby, BC, Canada 5 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada * These authors have contributed equally to this work Correspondence to: Yabin Cheng, email: chengyb@xmu.edu.cn Sunil Kalia, email: sunil.kalia@vch.ca Keywords: SERPINA3, melanoma, AACT (alpha-1 antichymotrypsin), tissue micro array, cell migration and invasion Received: November 14, 2015 Accepted: March 28, 2016 Published: May 17, 2016 ABSTRACT Serpin Peptidase Inhibitor, clade A member 3 (SERPINA3) was found to be abnormally overexpressed in a subset of melanoma tissue biopsies. High SERPINA3 expression was also associated with poor patient survival. In this study, we set out to test SERPINA3 protein’s prognostic potential with a larger-sized and independent patient cohort, and to explore SERPINA3’s function in melanoma cells. Tissue microarray-based immunohistochemistry analysis showed a significant increase in SERPINA3 expression in invasive and metastatic melanomas compared to normal nevi and melanoma-in-situ ( P < 0.001, Chi-square test). In melanoma patients, high SERPINA3 expression was strongly associated with worse overall and disease specific survival at 5 years. Multivariate Cox regression analysis showed that SERPINA3 expression is an independent prognostic factor to predict melanoma patient clinical outcome. When SERPINA3 expression was selectively silenced using small interfering RNA molecules (siRNA) in cultured melanoma cell lines, cell migration and matrix invasion was significantly decreased, but no change in cell proliferation was observed. This study confirms the prognostic potential of SERPINA3 expression in human cutaneous melanoma and reveals the pro-migration and pro-invasion functions of this protein on melanoma cells.