Reduced PDE4D7 in Prostate Cancer Correlates With Genomic Downregulation Within the Upstream PDE4D Coding Region

Abstract

Aim:PDE4D7 expression is significantly associated with prostate cancer (PCa) progression, representing an attractive prognostic biomarker. We sought to determine whether other genes in the PDE4D coding region were associated. Patients & methods: RNA from biopsy punch samples of resected tumor tissue was analyzed via RNA sequencing. RT-qPCR was used to determine PDE4D7 score. Results: Numerous genomic sequences within the PDE4D coding region on Chr5q12 revealed similar mRNA expression profiles to PDE4D7. PART1 had a significantly similar expression pattern to PDE4D7 across samples, correlating with disease progression. However, many other genes also exhibited matched expression to PDE4D7, including miRNAs and lncRNAs. Conclusion: These novel PDE4D7-associated genes, many of which are previously uncharacterized in cancer, represent putative PCa biomarkers and could have mechanistic roles in PCa progression.

Plain Language Summary

Identification of biological molecules that can indicate the presence of a disease are known as biomarkers and are valuable in medical research. For prostate cancer, the PDE4D7 gene is helpful for determining how the disease is getting worse. To understand more, this study explored whether genes located near PDE4D7 are also connected to prostate cancer. The analysis of tumor biopsies revealed that many of these nearby genes exhibited similar expression levels to PDE4D7, indicating their association with disease development. These findings suggest that several of these nearby genes could serve as potential biomarkers for prostate cancer by giving important clues to understand and detect the disease better.

Keywords:

• biomarkers
• cancer
• diagnostic
• genomics
• phosphodiesterase
• prognostic
• prostate
• stratification

Author contributions

C Gulliver, R Hoffmann analyzed the data. C Gulliver, GS Baillie, R Hoffmann wrote and reviewed the manuscript.

Acknowledgments

We acknowledge support provided by the University of Glasgow MVLS Doctoral Training Programme award to C Gulliver.

Financial & competing interests disclosure

This project was supported by the framework of CTMM (The Center for Translational Molecular Medicine; The Netherlands), PCMM project (grant no. 03O-203). R Hoffmann is an employee of Philips Research. R Hoffmann and GS Baillie hold patent rights relevant to the published work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.