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Updated: Nov 11, 2025
A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound
Published on: March 21, 2025
Single-cell Spatial Proteomic Revelations on the Multiparametric MRI Heterogeneity of Clinically Significant Prostate
Russell K Pachynski1, Eric H Kim2, Natalia Miheecheva3
1Molecular Oncology, Division of Oncology, Department of Medicine, Washington University, St Louis, Missouri.
Purpose:
Multiparametric MRI (mpMRI) has become an indispensable radiographic tool in diagnosing prostate cancer. However, mpMRI fails to visualize approximately 15% of clinically significant prostate cancer (csPCa). The molecular, cellular, and spatial underpinnings of such radiographic heterogeneity in csPCa are unclear.
Experimental Design:
We examined tumor tissues from clinically matched patients with mpMRI-invisible and mpMRI-visible csPCa who underwent radical prostatectomy. Multiplex immunofluorescence single-cell spatial imaging and gene expression profiling were performed. Artificial intelligence-based analytic algorithms were developed to examine the tumor ecosystem and integrate with corresponding transcriptomics.
Results:
More complex and compact epithelial tumor architectures were found in mpMRI-visible than in mpMRI-invisible prostate cancer tumors. In contrast, similar stromal patterns were detected between mpMRI-invisible prostate cancer and normal prostate tissues. Furthermore, quantification of immune cell composition and tumor-immune interactions demonstrated a lack of immune cell infiltration in the malignant but not in the adjacent nonmalignant tissue compartments, irrespective of mpMRI visibility. No significant difference in immune profiles was detected between mpMRI-visible and mpMRI-invisible prostate cancer within our patient cohort, whereas expression profiling identified a 24-gene stromal signature enriched in mpMRI-invisible prostate cancer. Prostate cancer with strong stromal signature exhibited a favorable survival outcome within The Cancer Genome Atlas prostate cancer cohort. Notably, five recurrences in the 8 mpMRI-visible patients with csPCa and no recurrence in the 8 clinically matched patients with mpMRI-invisible csPCa occurred during the 5-year follow-up post-prostatectomy.
Conclusions:
Our study identified distinct molecular, cellular, and structural characteristics associated with mpMRI-visible csPCa, whereas mpMRI-invisible tumors were similar to normal prostate tissue, likely contributing to mpMRI invisibility.
Insights
Multiparametric MRI (mpMRI) can miss some prostate cancers. mpMRI-invisible tumors share traits with normal tissue, unlike visible tumors, impacting diagnosis and potentially recurrence risk.
Area of Science:
- Oncology
- Radiology
- Genomics
Background:
- Multiparametric MRI (mpMRI) is crucial for prostate cancer diagnosis.
- Approximately 15% of clinically significant prostate cancer (csPCa) are not visualized by mpMRI.
- The reasons for this radiographic heterogeneity are not fully understood.
Purpose of the Study:
- To investigate the molecular, cellular, and spatial differences between mpMRI-visible and mpMRI-invisible csPCa.
- To understand the tumor microenvironment characteristics contributing to mpMRI invisibility.
Main Methods:
- Analysis of tumor tissues from patients with mpMRI-visible and mpMRI-invisible csPCa.
- Utilized multiplex immunofluorescence, single-cell spatial imaging, and gene expression profiling.
- Developed AI algorithms to analyze tumor ecosystem and transcriptomics.
Main Results:
- mpMRI-visible csPCa exhibited more complex epithelial architectures than mpMRI-invisible csPCa.
- mpMRI-invisible tumors showed stromal patterns similar to normal prostate tissue.
- No significant differences in immune cell infiltration or profiles were found between visible and invisible tumors.
- A 24-gene stromal signature enriched in mpMRI-invisible csPCa was identified, associated with favorable survival.
Conclusions:
- mpMRI-invisible csPCa possess distinct molecular and structural characteristics resembling normal prostate tissue.
- These differences likely explain why these tumors are not detected by mpMRI.
- The findings provide insights into the heterogeneity of prostate cancer detection and progression.
