Abstract: OBJECTIVE：To study the diagnostic value of sperm-associated antigen 9 (SPAG9) in urine combined with prostate-specific antigen density (PSAD)，free prostate-specific antigen (fPSA)/total PSA (tPSA) ratio in blood for the diagnosis of prostate cancer in the PSA grey zone. METHODS：From January 2018 to December 2022， 309 patients with serum PSA in the gray zone (4-10 ng/mL) who were admitted to the Second People's Hospital of Nantong were selected as the study subjects. They were divided into case and control groups： 58 prostate cancer case group and 251 benign cancer control group according to the pathological results of prostatocentesis. Before surgery， urine and blood samples from patients were collected and SPAG9，PSAD and fPSA/tPSA were determined. Differences in clinical data between the two groups were identified， and the related factors of prostate cancer were analyzed by logistic regression. The receiver operating characteristic curve (ROC) was drawn， and the area under the curve (AUC) was calculated. The diagnostic value of each indicator for prostate cancer in PSA gray zone was analyzed. RESULTS：Among the two groups of patients，there were no significant differences in body weight，tPSA，white blood cell count， hemoglobin，platelet count，total bilirubin，albumin，creatinine，uric acid and prostate volume between them (P>0.05). However，the age，urinary SPAG9，fPSA/tPSA and PSAD of the case group were significantly higher than those of the control group (P<0.05). Multivariate logistic regression analysis showed that SPAG9， fPSA/ tPSA and PSAD were related factors for prostate cancer. ROC curve analysis showed that SPAG9，fPSA/tPSA and PSAD alone and in combination could diagnose prostate cancer. The combined efficacy of the 3 indexes was ideal，and the sensitivity and specificity were 80.00% and 80.88% respectively. CONCLUSION：Urine SPAG9 can be used as a marker for the diagnosis of prostate cancer in PSA grey zone，and the combination of SPAG9，serum fPSA/tPSA and PSAD can provide good diagnostic efficacy.

Key words: prostate cancer, PSA gray area, sperm-associated antigen 9, prostate-specific antigen density, free PSA/total PSA ratio