Novel serum proteomic biomarkers for early diagnosis and aggressive grade identification of prostate cancer

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.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.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 (p<0.05) in Gleason 6 PCa when compared with BPH, and the concentration of osteopontin (SPP1) and ceruloplasmin (CP) increased with higher Gleason score.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.