Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma
Abstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study...
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-57533-w |
| _version_ | 1797247318218506240 |
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| author | Ying Wang Yongsheng Zhang Yanyan Li Jing Huang |
| author_facet | Ying Wang Yongsheng Zhang Yanyan Li Jing Huang |
| author_sort | Ying Wang |
| collection | DOAJ |
| description | Abstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study aimed to systematically analyze the changes of PDE4 enzyme family in THCA, and look for potential target for THCA therapy. We systematically analyzed the expression differences, prognostic value, genetic alteration, methylation modification, and the correlation with tumor immune microenvironment of PDE4 family in THCA using several public databases, including TCGA, GEO, GSCA, TNMplot, cBioPortal, DiseaseMeth and TIMER. Besides, functional enrichment analysis and protein–protein interaction (PPI) network of PDE4 family was investigated using Metascape and STRING databases. The expression levels of PDE4A, PDE4B and PDE4D were down-regulated in THCA patients at different cancer stages, while the expression level of PDE4C was significantly up-regulated. Moreover, THCA patients with higher PDE4C expression had shorter progress free survival compared with those with lower PDE4C expression. The low genomic alteration frequencies and mildly increased methylation levels of PDE4 family were found in THCA patients. Except for PDE4A, the expression levels of PDE4B, PDE4C and PDE4D could affect many immune cells infiltration during THCA progression. Four PDE4 subtypes were all enriched in cAMP catabolic process. Nevertheless, PDE4C was not enriched in the cAMP binding signal pathway, and PDE4B was not enriched in the G alphas signaling events. Notably, PDE4C participated in cAMP metabolic process by regulating adenylate cyclases (ADCYs), which involved ADCY1, ADCY5, ADCY6, ADCY8 and ADCY9. The findings of this study provide a partial basis for the role of PDE4 family in the occurrence and development of THCA. In addition, this study also suggested that PDE4C might be a potential prognostic marker of THCA, which could serve as a reference for future basic and clinical research. |
| first_indexed | 2024-04-24T19:56:47Z |
| format | Article |
| id | doaj.art-2b7529956105417b8cec89f8651a54bc |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:56:47Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2b7529956105417b8cec89f8651a54bc2024-03-24T12:16:54ZengNature PortfolioScientific Reports2045-23222024-03-0114111110.1038/s41598-024-57533-wElevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinomaYing Wang0Yongsheng Zhang1Yanyan Li2Jing Huang3Department of Laboratory Medicine, The First Hospital of Jilin UniversityCenter for Reproductive Medicine and Center for Prenatal Diagnosis, The First Hospital of Jilin UniversityDepartment of Laboratory Medicine, The First Hospital of Jilin UniversityDepartment of Laboratory Medicine, The First Hospital of Jilin UniversityAbstract Thyroid carcinoma (THCA) is the most common endocrine cancer. Phosphodiesterase (PDE) 4 enzyme family, as specific regulator of cyclic adenosine monophosphate, may play a important role in THCA. However, few studies on PDE4 enzyme family in THCA have been reported yet. Therefore, this study aimed to systematically analyze the changes of PDE4 enzyme family in THCA, and look for potential target for THCA therapy. We systematically analyzed the expression differences, prognostic value, genetic alteration, methylation modification, and the correlation with tumor immune microenvironment of PDE4 family in THCA using several public databases, including TCGA, GEO, GSCA, TNMplot, cBioPortal, DiseaseMeth and TIMER. Besides, functional enrichment analysis and protein–protein interaction (PPI) network of PDE4 family was investigated using Metascape and STRING databases. The expression levels of PDE4A, PDE4B and PDE4D were down-regulated in THCA patients at different cancer stages, while the expression level of PDE4C was significantly up-regulated. Moreover, THCA patients with higher PDE4C expression had shorter progress free survival compared with those with lower PDE4C expression. The low genomic alteration frequencies and mildly increased methylation levels of PDE4 family were found in THCA patients. Except for PDE4A, the expression levels of PDE4B, PDE4C and PDE4D could affect many immune cells infiltration during THCA progression. Four PDE4 subtypes were all enriched in cAMP catabolic process. Nevertheless, PDE4C was not enriched in the cAMP binding signal pathway, and PDE4B was not enriched in the G alphas signaling events. Notably, PDE4C participated in cAMP metabolic process by regulating adenylate cyclases (ADCYs), which involved ADCY1, ADCY5, ADCY6, ADCY8 and ADCY9. The findings of this study provide a partial basis for the role of PDE4 family in the occurrence and development of THCA. In addition, this study also suggested that PDE4C might be a potential prognostic marker of THCA, which could serve as a reference for future basic and clinical research.https://doi.org/10.1038/s41598-024-57533-wPhosphodiesterase 4Thyroid carcinomaCyclic-adenosine monophosphateBiomarkerPrognosis |
| spellingShingle | Ying Wang Yongsheng Zhang Yanyan Li Jing Huang Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma Scientific Reports Phosphodiesterase 4 Thyroid carcinoma Cyclic-adenosine monophosphate Biomarker Prognosis |
| title | Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| title_full | Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| title_fullStr | Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| title_full_unstemmed | Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| title_short | Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| title_sort | elevated pde4c level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma |
| topic | Phosphodiesterase 4 Thyroid carcinoma Cyclic-adenosine monophosphate Biomarker Prognosis |
| url | https://doi.org/10.1038/s41598-024-57533-w |
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