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Pan-Cancer Analysis of Cyclic Nucleotide Phosphodiesterases (PDEs) Expression, Variation, and Prognostic Significance
Zenghong Wu1, Huili Ren2, Feng Guo3
1Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
Abstract:
Dysregulation in the production of cyclic nucleotides and the upregulation of cyclic nucleotide phosphodiesterases (PDEs) are implicated in many tumor pathologies. Therefore, a comprehensive investigation of PDEs and their dysfunction across different cancers is necessary. In this study, we conducted an in-depth analysis of the genomic expression and variation profiles of PDEs across multiple cancer types. We found that PDE6C, PDE6D, PDE6H, and PDE7A were significantly upregulated in nearly all types of cancer, whereas PDE2A was downregulated in 15 cancer types. Our results demonstrated that somatic copy number alterations (SCNAs) and promoter DNA methylation in pan-cancer samples were heterogeneous and may regulate the expression of PDEs in tumors. We further observed that the expression of PDEs predominantly influences the prognosis of solid tumors. Five differentially expressed PDEs (PDE5A, PDE6D, PDE8A, PDE8B, and PDE9A) were identified as independent prognostic factors for patients with pan-cancer in both the training and testing cohorts. To our knowledge, this is the first study to construct a PDE signature in pan-cancer and to highlight the pivotal role of PDE4D in LIHC (liver hepatocellular carcinoma).
Insights
Cyclic nucleotide phosphodiesterases (PDEs) are crucial in cancer. This study reveals PDE dysregulation across cancers, identifying key PDEs like PDE4D as prognostic factors, especially in liver cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Dysregulation of cyclic nucleotides and upregulation of phosphodiesterases (PDEs) are linked to cancer.
- Understanding PDE dysfunction in various cancers is essential for therapeutic strategies.
Purpose of the Study:
- To comprehensively analyze PDE genomic expression and variation across multiple cancer types.
- To investigate the role of PDEs in tumor pathologies and patient prognosis.
Main Methods:
- In-depth analysis of genomic expression and variation profiles of PDEs in pan-cancer samples.
- Assessment of somatic copy number alterations (SCNAs) and promoter DNA methylation.
- Identification of differentially expressed PDEs as prognostic factors.
Main Results:
- PDE6C, PDE6D, PDE6H, and PDE7A were significantly upregulated in most cancers; PDE2A was downregulated in 15 cancer types.
- SCNAs and DNA methylation showed heterogeneous regulation of PDE expression in tumors.
- Five PDEs (PDE5A, PDE6D, PDE8A, PDE8B, PDE9A) were identified as independent prognostic factors for pan-cancer patients.
- PDE4D was highlighted for its pivotal role in liver hepatocellular carcinoma (LIHC).
Conclusions:
- PDEs are significantly dysregulated across various cancers, influencing tumor pathology.
- PDE expression profiles, particularly specific differentially expressed genes, serve as independent prognostic indicators in pan-cancer.
- This study establishes the first PDE signature in pan-cancer and underscores PDE4D's significance in LIHC.
