AHSP as a novel non-invasive urinary biomarker for prostate cancer

While prostate cancer (PCa) is a common malignant tumor in men, current tumor markers have poor specificity. Our previous exploratory research had identified alpha-hemoglobin–stabilizing protein (AHSP) as a potential novel tumor marker. This study aimed to investigate the expression and clinical significance of AHSP in PCa. AHSP levels in urine samples from patients with PCa, benign prostatic hyperplasia (BPH), urothelial carcinoma, or clear cell renal cell carcinoma (ccRCC) were determined using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical staining was performed on 101 PCa tissue samples to assess AHSP expression. Urinary proteomic profiling was employed to compare protein expression patterns in urothelial carcinoma and ccRCC to validate the PCa–specific AHSP expression. Immunohistochemical analysis revealed that AHSP was expressed in 93 (92.1%) PCa tissue samples. High AHSP expression showed a positive correlation with androgen receptor (AR) level (r = 0.353, p < 0.001). The incidence of high AHSP expression increased progressively with higher Gleason scores, and there was a significant difference between the Gleason 6–7 and 8–10 groups (57.4% vs. 83.0%, p = 0.005). AHSP expression was also positively correlated with Synaptophysin (Syn) expression (r = 0.332, p = 0.001), and AHSP was observed in normal neural ganglia. While the sensitivity of AHSP was slightly higher than that of prostate-specific antigen (PSA) (92.1% vs. 89.1%), the difference was not statistically significant. Urinary ELISA analysis demonstrated that the PCa group had the highest mean AHSP level (0.649 ± 0.055ng/ml), which was significantly higher than those in the BPH group (0.456 ± 0.058 ng/ml), the urothelial carcinoma group (0.446 ± 0.052 ng/ml), and the ccRCC group (0.438 ± 0.053 ng/ml) (all p < 0.0001). Notably, in urine samples, AHSP demonstrated significantly higher sensitivity than PSA (96.2% vs. 61.5%, p = 0.011). AHSP expression contributes to the diagnosis of PCa and is associated with tumor differentiation. Its positive correlation with AR expression and neuroendocrine differentiation suggests potential clinical relevance for treatment guidance. In urinary assays, AHSP exhibits higher sensitivity than PSA. AHSP exhibits relatively specific urinary expression in PCa, highlighting its potential as a noninvasive tumor biomarker.