Single-cell spatial proteomic revelations on the multiparametric MRI heterogeneity of clinically significant prostate cancer

Russell K. Pachynski, Eric H. Kim, Natalia Miheecheva, Nikita Kotlov, Akshaya Ramachandran, Ekaterina Postovalova, Ilia Galkin, Viktor Svekolkin, Yang Lyu, Qiong Zou, Dengfeng Cao, Joseph Gaut, Joseph E. Ippolito, Alexander Bagaev, Maria Bruttan, Olga Gancharova, Krystle Nomie, Maria Tsiper, Gerald L. Andriole, Ravshan AtaullakhanovJames J. Hsieh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


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.

Original languageEnglish
Pages (from-to)3478-3490
Number of pages13
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 2021


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