Background: Sex hormone-binding globulin (SHBG) is a dimeric glycoprotein synthesized in, and secreted from, hepatocytes. SHBG is also expressed in, but not secreted from, the prostate, where its role is unclear. The expression of SHBG is linked to lipid metabolism, and it also modulates transport and availability of androgen. Given its expression in the prostate and role in the androgen signalling axis, we postulated that expression of SHBG will increase in prostate cancer (PCa), distinguishing it from both normal prostate and benign prostate hyperplasia (BPH), and reflect aggressiveness of disease.
Methods: We utilized tissues and data from existing South Australian PCa Registries. SHBG mRNA was measured by qRT-PCR (n=47: 7 BPH and 40 PCa of varying Gleason score (GS)). SHBG protein was measured by immunohistochemistry and quantified by Image J software (n=125: 8 normal, 32 BPH and 85 PCa of varying GS). The expression of SHBG transcript variants was analysed by qRT-PCR from an independent set of PCa samples of varying GS (n=12 1 with GS ≤6, 9 with GS ~7 and 2 with GS ≥8) that had been treated with the androgen receptor antagonist Enzalutamide (10 uM MDV) or vehicle control.
Results: SHBG mRNA and SHBG protein are barely detectable in normal prostate epithelium or in BPH but increase in PCa epithelial cells (P<0.001; compared to both). SHBG protein concentration was highest in with GS ≥ 8 compared to GS ≤ 6 and ~7 (P=0.002). PCa with GS ≤6 (n=1) and GS ≥ 8 (n=2) expressed unique coding transcripts of 1382bp and 1311bp respectively. However, within PCa of GS~ 7(n=9), there was marked heterogeneity of SHBG transcripts; 463 bp, 522 bp (non-coding), 526bp and 1146bp transcripts predominated, none expressed the 1311 bp and 1382 bp transcript. In response to 10 uM MDV, PCa with GS ≤ 6 (n=1) did not express, 522 bp transcript predominated in GS ≥ 8 (n=2) while GS ≥ 7 (n=9) expressed unique coding transcripts of 1382bp and 973bp respectively but 522 bp transcript predominated.
Conclusions: SHBG protein abundance and/or transcript size are markers of advanced disease and may be a novel marker for aggressive tumor behavior in early-stage disease.
18 - 21 May 2019
European Society of Endocrinology