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Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection

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Spatial Transcriptomic Profiling to Characterize the Nature of Peripheral- Versus Transition-zone Prostate Cancer.

Parth Patel¹, Srinivas Nallandhighal¹, David Scoville²

¹Department of Urology, Michigan Medicine, Ann Arbor, MI, USA.

European Urology Focus

|November 29, 2024

Summary

Prostate cancer in the transition zone (TZ) shows higher androgen response signaling (ARS), explaining elevated PSA and better prognosis compared to peripheral zone (PZ) tumors. These findings may improve PC diagnosis and treatment strategies.

Keywords:

Peripheral-zone prostate cancer Prognosis Prostate cancer Prostate-specific antigen Survival Transition-zone prostate cancer

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Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer

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Published on: November 2, 2013

Area of Science:

Oncology
Molecular Biology
Genomics

Background:

Prostate cancer (PC) originating in the transition zone (TZ) typically presents with higher prostate-specific antigen (PSA) levels but a better prognosis than peripheral zone (PZ) PC.
The molecular mechanisms underlying these zonal differences in PC remain incompletely understood.

Purpose of the Study:

To investigate the molecular distinctions between TZ and PZ prostate tumors.
To elucidate the clinical implications of these zonal molecular differences.

Main Methods:

Spatial whole-transcriptome analysis was performed on 50 regions of interest from three patients with PZ and/or TZ PC.
Differential gene expression and pathway enrichment analyses were conducted.
Survival analyses utilized The Cancer Genome Atlas (TCGA) prostate dataset.

Main Results:

Distinct gene expression profiles were identified between PZ and TZ tumors.
TZ tumors demonstrated enrichment of androgen response signaling (ARS) and higher androgen pathway activity, irrespective of tumor grade or cellular composition.
Genes underexpressed in PZ tumors, including ARS genes, correlated with poorer progression-free survival in TCGA data.

Conclusions:

Higher ARS in TZ tumors explains the elevated PSA levels and better clinical outcomes observed in patients with TZ PC.
Zonal location and associated molecular profiles, particularly ARS, are critical factors in PC prognosis.
Integrating zonal information into PC diagnostic and treatment algorithms warrants further investigation.