Low circulating levels of the mitochondrial-peptide hormone SHLP2: novel biomarker for prostate cancer risk

CONTEXT: Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule. OBJECTIVE: To determine whether serum SHLP2 concentration is associated with PCa risk and whether associations are race-specific. Design, Setting and Participants: Patients undergoing prostate biopsy were recruited from the Durham Veterans Affairs hospital. Serum was collected prior to biopsy and SHLP2 measured by ELISA. We selected 200 men for analysis (100 negative biopsies and 100 PCa cases; 100 black and 100 white). RESULTS: Mean SHLP2 levels were significantly higher in white controls versus black controls and SHLP2 was significantly higher in white controls versus white PCa cases. In contrast, there was no significant difference in SHLP2 levels between black controls and black cases. SHLP2 levels > 350-pg/ml ruled out PCa with ≥ 95% accuracy in both races. CONCLUSIONS: Lower SHLP2 was linked with increased PCa risk in white men, but no significant association was observed in black men. While SHLP2 > 350-pg/ml ruled out PCa in both races with high accuracy, SHLP2 was unrelated to PCa grade. These data suggest the circulating mitochondrial-derived peptide hormone, SHLP2 plays a key role in the development and racial disparity of prostate cancer.