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• W2523844590 abstract "1098 Background: Recently TOP2A alteration was found to be a predictor for ATC-CT and our neural network analysis of BC gene expression array (GEA) data has revealed SPAG5 gene as a major hubs in both TOP2A and proliferation pathways. In this study the molecular and clinicopathological functions of SPAG5 was investigated in BC and OVC. Methods: (1) A series of 171 BC was evaluated for SPAG5 gene copy number (using aCGH) and mRNA expression (using GEA) which were validated in 5 independent databases. (2) The expression of SPAG5 protein was evaluated pre-clinically in BC and OVC cell lines and in both 40 normal breast tissues and a series of 1650 primary BC and was correlated to clinicopathological and other biomarkers. (3) The association between SPAG5 and response to CT was investigated in a) 350 ER negative BC treated with adjuvant ATC-CT, b) 250 BC treated with neoadjuvant (NEO-A)-ATC-CT, and c) 200 primary OVC treated with cisplatinum based adjuvant CT. Results: (1) 5% and 15% of the 171 BC showed amplification and gain of SPAG5 locus, respectively, at 17q11.2. SPAG5 mRNA expression displayed a significant correlation with its copy number (p< 0.0001). (2) 30% and 20% of ovarian and BC respectively, showed overexpression of SPAG5 protein (+). In BC, SPAG5+ at both mRNA and protein levels showed a significant association with aggressive phenotypes, high mitosis, ER-, high grade, p53 mutation and epithelial mesenchymal transition phenotypes (ps <0.0001). SPAG5 mRNA (+) was statistically associated with poor survivals (p<0.0001). (3) In ER- BC treated with adjuvant ATC-CT, SPAG5 negative (-)had 7-times higher risk of progression compared with SPRAG+ BC (p<0.0001). SPAG5+ BC received NEO-A-ATC based CT achieved 38% pathological complete response (pCR) vs. 6% of SPAG5- (p<0.0001). After controlling to other predictors for pCR, SPAG5 was an independent predictor (HR; 2.4; p=0.001). Similarly, SPAG5- OVCs were resistant to platinum (p<0.001) and independently associated with poor survival (p<0.001). Conclusions: SPAG5 is an important novel gene implicated in the survival of BC and OVC cells and its protein expression is an independent predictor for anthracycline/ cisplatinum CT." @default.
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• W2523844590 date "2012-05-20" @default.
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• W2523844590 title "A study of sperm-associated antigen 5 (SPAG5) in predicting response to anthracycline (ATC)/platinum chemotherapies (CT) in breast (BC) and ovarian cancers (OVC)." @default.
• W2523844590 doi "https://doi.org/10.1200/jco.2012.30.15_suppl.1098" @default.
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