Novel Serum Proteomic Biomarkers for Early Diagnosis and Aggressive Grade Identification of Prostate Cancer

Background: Prostate cancer (PCa) is one of the most common tumors and the second leading cause of cancer-related death in men. The discovery of novel biomarkers for PCa diagnosis in the early stage, as well as discriminating aggressive PCa from non-aggressive PCa continue to pose a challenge. The aim of this study was to identify serum proteins that were sensitive and specific enough to detect early-stage and aggressive PCa.

Methods: The serum proteomic profiling of patients with PCa and benign prostatic hyperplasia (BPH) was comprehensively analyzed using data-independent acquisition mass spectrometry (DIA-MS), and the bioinformatics analysis was performed. The differentially expressed proteins (DEPs) of interest were further verified by enzyme-linked immunosorbent assay (ELISA) and immunoturbidimetry assay.

Results: Statistically significant difference in abundance showed 56 DEPs between early-stage PCa and BPH and 47 DEPs between aggressive and non-aggressive PCa patients. In addition, the verification results showed that serum L-selectin concentration was significantly higher (<0.05) in Gleason 6 PCa when compared with BPH, and the concentration of osteopontin (SPP1) and ceruloplasmin (CP) increased with higher Gleason score.

Conclusions: DIA-MS has great potential in cancer-related biomarker screening. Our data demonstrated that adding SPP1 and CP to PSA improved the separation of Gleason 7 (4 + 3) or above from Gleason 7 (3 + 4) or below compared with PSA diagnosis alone. Serum SPP1 and CP could be effective biomarkers to differentiate aggressive PCa (especially Gleason 7 (4 + 3) or above) from non-aggressive disease.