Evaluation of plasma GDF15 and a predictive nomogram for prostate cancer diagnosis

Prostate-specific antigen (PSA) has limited specificity in prostate cancer screening, highlighting the need for novel circulating biomarkers to improve diagnostic accuracy. This study aimed to identify candidate biomarkers through preliminary proteomic screening, evaluate the diagnostic potential of plasma growth differentiation factor 15 (GDF15), and develop a diagnostic prediction model for prostate cancer. This observational study enrolled patients hospitalized in the urology department for prostate-related conditions who were scheduled to undergo prostate biopsy. Patients were classified according to biopsy pathology into prostate cancer and non-prostate cancer groups; the latter consisted of biopsy-indicated patients with benign prostatic conditions rather than healthy controls. Preliminary proteomic screening of TiO₂-enriched plasma fractions was used to nominate candidate proteins. The diagnostic performance of these candidates was subsequently evaluated by enzyme-linked immunosorbent assay (ELISA) in unfractionated plasma from the main biopsy-indicated cohort. Receiver operating characteristic (ROC) curves were used to assess diagnostic performance. Multivariate logistic regression was performed to evaluate independent associations with prostate cancer risk, and a nomogram prediction model was subsequently constructed. A total of 312 patients were included, comprising 132 patients with biopsy-confirmed prostate cancer and 180 patients without pathological evidence of prostate cancer. Plasma GDF15 and SLPI levels were significantly higher in the prostate cancer group than in the non-cancer group ( P < 0.001). Multivariate analysis demonstrated that GDF15 and SLPI were independently associated with prostate cancer risk. ROC analysis showed that GDF15 achieved an area under the curve (AUC) of 0.805. A nomogram incorporating GDF15, age, body mass index (BMI), and total prostate-specific antigen (tPSA) demonstrated strong predictive performance, with AUCs of 0.887 and 0.874 in the training and validation cohorts, respectively. Plasma GDF15 showed promising diagnostic performance for prostate cancer in this biopsy-indicated cohort. A nomogram integrating GDF15 with clinical variables demonstrated favorable internal diagnostic performance. However, the limited number of patients with tPSA levels of 4–10 ng/mL precluded reliable subgroup analysis in this clinically important range, and further validation in larger cohorts is warranted.