Fig. 7
Pre-operative serum levels of prosaposin (PSAP) are significantly higher in breast cancer patients whose disease subsequently recurred. High levels of both PSAP and androgen receptor (AR) mRNA are very strongly associated with poor disease-free survival (DFS) in endocrine-treated breast cancer. a A commercially available ELISA kit for human PSAP was used to quantify serum levels of the secreted protein in sera from breast cancer patients. PSAP levels were evaluated in a subset of endocrine-resistant patients versus age-matched controls. (i) The non-recurrent control group was used to generate a training set to establish a cutoff value of 0.84 ng/μl (median + 2 SD) to distinguish between patients sensitive and resistant to endocrine therapy (dashed horizontal line). The median follow up of the cohort was 35 months. Preliminary findings indicate approximately 35 % of postmenopausal breast cancer patients who had recurrent disease whilst on endocrine therapy expressed PSAP serum levels elevated above the cutoff (p = 0.04). (ii) Levels of PSAP detected in sera from patients with recurrent breast cancer was significantly higher than those of endocrine-responsive patients (p = 0.03). b (i) Breast cancer patients (The Cancer Genome Atlas dataset (TGCA) with high androgen receptor (AR) expression (upper quartile) were selected and Spearman’s correlation between HOXC11 and PSAP was calculated for each subtype: gray luminal A, blue luminal B, red basal, green HER2 (n = 199). (ii) Tabulated results show Spearman’s correlation between HOXC11 and PSAP mRNA in AR-high breast cancers per subtype. c (i) Meta-analysis of transcript levels in breast cancer patients (n = 661) indicates that PSAP mRNA is a significant predictor of poor response to endocrine treatment in endocrine-treated patients (p = 0.03; hazard ratio (HR) 1.4). (ii) Patients expressing high mRNA levels of both PSAP and AR experience much shorter periods of DFS reflected in an HR of 2.2 (p = 0.0003). BrCa breast cancer, HER2 human epidermal growth factor 2