Analysis of risk factors for MRI-invisible prostate cancer—the significance of AGGF1 immunohistochemical detection and PSAD

Jingcheng Lyu^1,2,#, Ruiyu Yue^1,2,#, Ye Tian^1,2,*, Boyu Yang^1,2,*
1 Department of Urology, Capital Medical University, Beijing Friendship Hospital, Beijing, China
2 Institute of Urology, Beijing Municipal Health Commission, Beijing, China
* Corresponding Author: Ye Tian. Email: email ; Boyu Yang. Email: email
# Jingcheng Lyu and Ruiyu Yue are co-first authors
(This article belongs to the Special Issue: Advancing Early Detection of Prostate Cancer: Innovations, Challenges, and Future Directions)

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.074814

Received 18 October 2025; Accepted 14 January 2026; Published online 21 February 2026

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Abstract

Objectives: Patients with a multi-parameter magnetic resonance imaging (mpMRI) prostate imaging report and data system (PI-RADS) score ≤ 3, but with clinically significant prostate cancer (CSPCa) detected by biopsy, are termed MRI-Invisible prostate cancer (MRI(-)PCa). This study aims to explore risk factors for MRI(-)PCa and identify immunohistochemical indicators with predictive significance. Methods: A retrospective analysis was conducted on 376 patients with PI-RADS score ≤ 3 who underwent 24-needle systematic prostate biopsy at Beijing Friendship Hospital, Capital Medical University (January 2015 to October 2025). Clinical data, imaging data, and Angiogenic factor with G and FHA domain 1 (AGGF1) immunohistochemical results were collected. Patients were grouped into CSPCa (n = 102) and non-CSPCa (n = 274). t-tests, rank sum tests, and χ² tests were used for univariate analysis, followed by multivariate Logistic regression to determine independent risk factors. Receiver Operating Characteristic (ROC) curves were drawn. Subgroup analyses were conducted based on prostate-specific antigen (PSA) status and PI-RADS score using the same statistical methods. Moreover, we also used the Kruskal-Wallis test to compare the differences in AGGF1 expression percentages across different Gleason score groups according to ISUP in CSPCa patients. Results: Multivariate Logistic regression analysis showed that prostate-specific antigen density (PSAD) [OR: 0.971, 95%CI: 0.952, 0.991] and high expression of AGGF1 [OR: 1.065, 95%CI: 1.022, 1.109] were independent risk factors for MRI(-)PCa (p < 0.05). Meanwhile, when the PSAD of the patient is more than 0.25 ng/mL/cm³, it is necessary to be more suspicious that the patient may have prostate cancer (p < 0.05), and an AGGF1 immunohistochemical analysis should be conducted after the biopsy. In the PSA-negative subgroup, only high AGGF1 expression was an independent risk factor (p < 0.05). In the PSA-positive subgroup, PSAD [OR: 0.500, 95%CI: 0.279, 0.895] and AGGF1 [OR: 1.064, 95%CI: 1.037, 1.092] results were independent risk factors (p < 0.05). In subgroup analyses for PI-RADS 1-2 and PI-RADS 3, both PSAD and AGGF1 were accurate predictors of CSPCa (p < 0.05). Among all CSPCa patients, in the Gleason score 3 + 3 group, the average AGGF1 expression percentage of the patients was 48.60% ± 11.03%, which was significantly lower than that of the Gleason score 4 + 3 group (61.00% ± 6.12%) and the Gleason score 4 + 4 group (71.01% ± 4.46%), and the differences were statistically significant (p < 0.001). Conclusions: For patients with a PI-RADS score ≤ 3, attention should be paid to PSAD before biopsy, especially for those patients with PSAD > 0.25 ng/mL/cm³, not just PSA levels. After biopsy, AGGF1 immunohistochemical staining can be supplemented to help determine the risk and the malignancy of CSPCa.