title: Up-regulation of SERPINA3 correlates with high mortality of melanoma patients and increased migration and invasion of cancer cells.
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.
authors.affiliation: Faculty of Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Xiamen University, Xiamen, China.|Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Welichem Biotech Inc, Burnaby, BC, Canada.
authors.forename: Liren
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kalia
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002465:Cell Movement / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016016:Proportional Hazards Models; D015843:Serpins / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000473:pathology*; D046888:Tissue Array Analysis; D015854:Up-Regulation; D000096142:Cutaneous Malignant Melanoma
chemical_list: D014408:Biomarkers, Tumor; C516148:SERPINA3 protein, human; D015843:Serpins
keywords: AACT (alpha-1 antichymotrypsin); SERPINA3; cell migration and invasion; melanoma; tissue micro array