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Updated: Jul 5, 2026
miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
Expression of microRNAs and protein-coding genes associated with perineural invasion in prostate cancer
Robyn L Prueitt1, Ming Yi, Robert S Hudson
1Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland 20892-4258, USA.
Background:
Perineural invasion (PNI) is the dominant pathway for local invasion in prostate cancer. To date, only few studies have investigated the molecular differences between prostate tumors with PNI and those without it.
Methods:
To evaluate the involvement of both microRNAs and protein-coding genes in PNI, we determined their genome-wide expression with a custom microRNA microarray and Affymetrix GeneChips in 50 prostate adenocarcinomas with PNI and 7 without it. In situ hybridization (ISH) and immunohistochemistry was used to validate candidate genes.
Results:
Unsupervised classification of the 57 adenocarcinomas revealed two clusters of tumors with distinct global microRNA expression. One cluster contained all non-PNI tumors and a subgroup of PNI tumors. Significance analysis of microarray data yielded a list of microRNAs associated with PNI. At a false discovery rate (FDR)<10%, 19 microRNAs were higher expressed in PNI tumors than in non-PNI tumors. The most differently expressed microRNA was miR-224. ISH showed that this microRNA is expressed by perineural cancer cells. The analysis of protein-coding genes identified 34 transcripts that were differently expressed by PNI status (FDR<10%). These transcripts were down-regulated in PNI tumors. Many of those encoded metallothioneins and proteins with mitochondrial localization and involvement in cell metabolism. Consistent with the microarray data, perineural cancer cells tended to have lower metallothionein expression by immunohistochemistry than nonperineural cancer cells.
Conclusions:
Although preliminary, our findings suggest that alterations in microRNA expression, mitochondrial function, and cell metabolism occur at the transition from a noninvasive prostate tumor to a tumor with PNI.
Insights
Prostate cancer with perineural invasion (PNI) shows distinct microRNA and gene expression changes, particularly in metallothioneins and mitochondrial metabolism, differentiating it from non-invasive tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Perineural invasion (PNI) is a primary route for prostate cancer local spread.
- Limited research exists on molecular distinctions between prostate tumors with and without PNI.
Purpose of the Study:
- To investigate the roles of microRNAs and protein-coding genes in prostate cancer PNI.
- To identify molecular markers associated with PNI in prostate adenocarcinoma.
Main Methods:
- Genome-wide expression analysis using microRNA microarrays and Affymetrix GeneChips on 57 prostate adenocarcinomas (50 with PNI, 7 without).
- Validation of candidate genes through in situ hybridization (ISH) and immunohistochemistry (IHC).
Main Results:
- Two distinct microRNA expression clusters identified, with one containing all non-PNI tumors.
- 19 microRNAs were significantly upregulated in PNI tumors (FDR<10%), with miR-224 being the most prominent.
- 34 protein-coding transcripts were downregulated in PNI tumors (FDR<10%), including metallothioneins and mitochondrial proteins.
Conclusions:
- Alterations in microRNA expression are associated with PNI in prostate cancer.
- Changes in mitochondrial function and cell metabolism are implicated in the transition to invasive prostate tumors.
- Findings suggest potential molecular targets for understanding and potentially treating PNI.
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