Evaluation of S100A4, CA-12, CA-9, Annexin A1/A2, and Galectin-3 in Prostate Cancer: Diagnostic and Prognostic Implications.
The limited specificity of prostate-specific antigen (PSA) increases the risk of unnecessary biopsies and overtreatment. This study aimed to evaluate the diagnostic and prognostic value of serum S100A4, along with CA-9, CA-12, Annexin A1/A2, and Galectin-3, in prostate cancer.
This prospective case-control study, conducted between July 2024 and September 2025, included 80 patients with histopathologically confirmed prostate cancer and 40 age-matched healthy controls. Patients were stratified into low-risk (ISUP grades 1-2) and high-risk (ISUP ≥3) groups. Serum biomarker levels were measured using ELISA. Diagnostic and prognostic performance was assessed by receiver operating characteristic (ROC) analysis, with cut-off values determined using the Youden index. Logistic regression analyses were performed to identify independent biomarkers.
Serum CA-12 and CA-9 levels were significantly higher in prostate cancer patients than in controls (p = 0.004 and p = 0.032, respectively). Although S100A4 levels were lower in prostate cancer patients compared with controls, they were significantly higher in high-risk patients within the cancer cohort (p = 0.002). Logistic regression identified S100A4 (p = 0.032) and CA-12 (p = 0.004) as independent predictors of prostate cancer diagnosis. ROC analysis demonstrated excellent diagnostic accuracy for CA-12 (>52.9 ng/mL; AUC = 0.99) and S100A4 (<9.96 ng/mL; AUC = 0.98). For prognostic stratification, S100A4 (>8.27 ng/mL; AUC = 0.97) and CA-12 (>72.8 ng/mL; AUC = 0.91) effectively distinguished high-risk from low-risk disease.
S100A4 and CA-12 exhibit strong diagnostic and prognostic performance in prostate cancer. When used alongside PSA, S100A4 and CA-12 may improve risk stratification in patients with suspected prostate cancer and help reduce unnecessary prostate biopsies.
This prospective case-control study, conducted between July 2024 and September 2025, included 80 patients with histopathologically confirmed prostate cancer and 40 age-matched healthy controls. Patients were stratified into low-risk (ISUP grades 1-2) and high-risk (ISUP ≥3) groups. Serum biomarker levels were measured using ELISA. Diagnostic and prognostic performance was assessed by receiver operating characteristic (ROC) analysis, with cut-off values determined using the Youden index. Logistic regression analyses were performed to identify independent biomarkers.
Serum CA-12 and CA-9 levels were significantly higher in prostate cancer patients than in controls (p = 0.004 and p = 0.032, respectively). Although S100A4 levels were lower in prostate cancer patients compared with controls, they were significantly higher in high-risk patients within the cancer cohort (p = 0.002). Logistic regression identified S100A4 (p = 0.032) and CA-12 (p = 0.004) as independent predictors of prostate cancer diagnosis. ROC analysis demonstrated excellent diagnostic accuracy for CA-12 (>52.9 ng/mL; AUC = 0.99) and S100A4 (<9.96 ng/mL; AUC = 0.98). For prognostic stratification, S100A4 (>8.27 ng/mL; AUC = 0.97) and CA-12 (>72.8 ng/mL; AUC = 0.91) effectively distinguished high-risk from low-risk disease.
S100A4 and CA-12 exhibit strong diagnostic and prognostic performance in prostate cancer. When used alongside PSA, S100A4 and CA-12 may improve risk stratification in patients with suspected prostate cancer and help reduce unnecessary prostate biopsies.
Authors
Aslan Aslan, Huyut Huyut, Keleş Keleş, Bedir Bedir, Eryılmaz Eryılmaz, Huyut Huyut, Saygın Saygın, Demir Demir, Taken Taken
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