Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma
Melanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Current Issues in Molecular Biology |
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| Online Access: | https://www.mdpi.com/1467-3045/44/9/282 |
| _version_ | 1827662277450399744 |
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| author | Nehal Farid El-Helbawy Ahmed Ezat El Zowalaty |
| author_facet | Nehal Farid El-Helbawy Ahmed Ezat El Zowalaty |
| author_sort | Nehal Farid El-Helbawy |
| collection | DOAJ |
| description | Melanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, the bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identifies the significant upregulation of extra-cellular matrix and cellular adhesion genes in young cohorts, while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 are significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration are differentially expressed. The differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism is also observed. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes in melanoma, and novel therapeutic targets for future studies. |
| first_indexed | 2024-03-10T00:22:50Z |
| format | Article |
| id | doaj.art-752ae76ef841462e991f96c4c36ccc7b |
| institution | Directory Open Access Journal |
| issn | 1467-3037 1467-3045 |
| language | English |
| last_indexed | 2024-03-10T00:22:50Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | Current Issues in Molecular Biology |
| spelling | doaj.art-752ae76ef841462e991f96c4c36ccc7b2023-11-23T15:39:17ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452022-09-014494118413110.3390/cimb44090282Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary MelanomaNehal Farid El-Helbawy0Ahmed Ezat El Zowalaty1Department of Anatomy and Embryology, Faculty of Medicine, Tanta University, Tanta 31111, EgyptSahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, University of Gothenburg, 40530 Gothenburg, SwedenMelanoma is a lethal form of skin cancer. Immunotherapeutic agents such as anti-PD-1 (pembrolizumab and nivolumab) and anti-CTLA-4 (ipilimumab) have revolutionized melanoma treatment; however, drug resistance is rapidly acquired. Several studies have reported an increase in melanoma rates in older patients. Thus, the impact of ageing on transcriptional profiles of melanoma and response to immunotherapy is essential to understand. In this study, the bioinformatic analysis of RNA seq data of old and young melanoma patients receiving immunotherapy identifies the significant upregulation of extra-cellular matrix and cellular adhesion genes in young cohorts, while genes involved in cell proliferation, inflammation, non-canonical Wnt signaling and tyrosine kinase receptor ROR2 are significantly upregulated in the old cohort. Several Treg signature genes as well as transcription factors that are associated with dysfunctional T cell tumor infiltration are differentially expressed. The differential expression of several genes involved in oxidative phosphorylation, glycolysis and glutamine metabolism is also observed. Taken together, this study provides novel findings on the impact of ageing on transcriptional changes in melanoma, and novel therapeutic targets for future studies.https://www.mdpi.com/1467-3045/44/9/282melanomaageingRNA-seqtranscriptional profilesgene expressionimmunotherapy |
| spellingShingle | Nehal Farid El-Helbawy Ahmed Ezat El Zowalaty Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma Current Issues in Molecular Biology melanoma ageing RNA-seq transcriptional profiles gene expression immunotherapy |
| title | Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma |
| title_full | Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma |
| title_fullStr | Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma |
| title_full_unstemmed | Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma |
| title_short | Identification of Age-Associated Transcriptomic Changes Linked to Immunotherapy Response in Primary Melanoma |
| title_sort | identification of age associated transcriptomic changes linked to immunotherapy response in primary melanoma |
| topic | melanoma ageing RNA-seq transcriptional profiles gene expression immunotherapy |
| url | https://www.mdpi.com/1467-3045/44/9/282 |
| work_keys_str_mv | AT nehalfaridelhelbawy identificationofageassociatedtranscriptomicchangeslinkedtoimmunotherapyresponseinprimarymelanoma AT ahmedezatelzowalaty identificationofageassociatedtranscriptomicchangeslinkedtoimmunotherapyresponseinprimarymelanoma |