title: Prognostic significance of the expression of nuclear eukaryotic translation initiation factor 5A2 in human melanoma.
abstract: Eukaryotic translation initiation factor 5A2 (EIF5A2) expression is upregulated in various cancers. The present authors previously demonstrated that cytoplasmic EIF5A2 expression increases with melanoma progression and inversely correlates with patient survival. Other studies have suggested that nuclear EIF5A2 may also play a role in oncogenesis. The present study used immunohistochemistry and tissue microarray with a large number of melanocytic lesions (n=459) and demonstrated that nuclear EIF5A2 expression was significantly upregulated between common acquired nevi, dysplastic nevi and primary melanomas, and between primary melanomas and metastatic melanomas. Nuclear EIF5A2 expression was inversely associated with overall and disease-specific 5-year survival rate for all (P<0.001) and primary (P=0.014 and P=0.015, respectively) melanoma patients. Nuclear EIF5A2 expression was directly associated with melanoma thickness (P=0.036) and American Joint Committee on Cancer staging (P<0.001), which suggests the possible role of nuclear EIF5A2 in melanoma cell invasion. Subsequently, the present study investigated the association between the expression of nuclear EIF5A2 and matrix metalloproteinase-2 (MMP-2), which is an important factor for promoting cancer cell invasion. Nuclear EIF5A2 and a strong MMP-2 expression were directly associated, and their concurrent expression was significantly associated with a poorer overall and disease-specific 5-year survival rate for all and primary melanoma patients. Nuclear and cytoplasmic EIF5A2 expression were also demonstrated to be significantly associated, and simultaneous expression of the two forms of EIF5A2 was significantly associated with poor overall and disease-specific 5-year survival rates for all and primary melanoma patients. Multivariate Cox regression analysis revealed that nuclear EIF5A2 expression alone and in combination with cytoplasmic EIF5A2 expression was an adverse independent prognostic factor for all and primary melanoma patients. In conclusion, the present study for the first time, to the best of our knowledge, demonstrated that nuclear EIF5A2 expression is an independent prognostic marker in melanoma, and revealed its role in melanoma progression and patient survival. Therefore, nuclear EIF5A2 may have the potential to serve as a therapeutic marker for melanoma.
authors.affiliation: Department of Dermatology and Skin Science, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada; Department of Surgery, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada.
authors.forename: Shahram
authors.initials: S
authors.lastname: Khosravi
authors.affiliation: Department of Pathology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.affiliation: Department of Dermatology and Skin Science, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Surgery, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC V5Z 1L8, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ong
keywords: melanoma; nuclear EIF5A2; patient survival; prognostic factor