Loss of SNF5 expression correlates with poor patient survival in melanoma.
OBJECTIVE
Aberrant expression of SWI/SNF chromatin remodeling complex is involved in cancer development. The tumor suppressor SNF5, the core subunit of SWI/SNF complex, has been shown to regulate cell differentiation, cell cycle control, and apoptosis. To investigate the role of SNF5 in the development of melanoma, we examined the expression of SNF5 in melanocytic lesions at different stages and analyzed the correlation between SNF5 expression and clinicopathologic variables and patient survival.


METHODS
Using tissue microarray and immunohistochemistry, we evaluated SNF5 staining in 51 dysplastic nevi, 88 primary melanomas, and 48 metastatic melanomas. We studied chemosensitivity of melanoma cells with reduced SNF5 expression by siRNA using cell survival and apoptosis assays.


RESULTS
SNF5 expression was reduced in metastatic melanoma compared with dysplastic nevi (P = 0.005), in advanced primary melanoma (Clark's level V) compared with low risk Clark's level II melanoma (P = 0.019), and in melanoma at sun-exposed sites compared with sun-protected sites (P = 0.044). Furthermore, we showed a strong correlation between negative SNF5 expression and a worse 5-year survival in melanoma patients (P = 0.016). Multivariate Cox regression analysis revealed that negative SNF5 expression is an independent prognostic factor to predict patient outcome in primary melanomas (P = 0.031). Finally, we showed that knockdown of SNF5 in melanoma cell lines resulted in significant chemoresistance.


CONCLUSIONS
Our data indicate that SNF5 may be an important marker for human melanoma progression and prognosis as well as a potential therapeutic target.
Lin
Hanyang
H
Department of Dermatology, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada.
Wong
Ronald P C
RP
Martinka
Magdalena
M
Li
Gang
G
D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008545:Melanoma / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D000071796:SMARCB1 Protein; D012878:Skin Neoplasms / Q000378:metabolism* / Q000401:mortality; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism*
D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors