TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma
The present study was the first comprehensive investigation of genetic mutation and expression levels of the p53 signaling genes in cutaneous melanoma through various genetic databases providing large datasets. The mutational landscape of p53 and its signaling genes was higher than expected, with TP...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2023-08-01
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| Series: | Cancer Informatics |
| Online Access: | https://doi.org/10.1177/11769351231177267 |
| _version_ | 1797687468247482368 |
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| author | Safir Ullah Khan Zahid Ullah Hadia Shaukat Shiza Unab Saba Jannat Waqar Ali Amir Ali Muhammad Irfan Muhammad Fiaz Khan Rodolfo Daniel Cervantes-Villagrana |
| author_facet | Safir Ullah Khan Zahid Ullah Hadia Shaukat Shiza Unab Saba Jannat Waqar Ali Amir Ali Muhammad Irfan Muhammad Fiaz Khan Rodolfo Daniel Cervantes-Villagrana |
| author_sort | Safir Ullah Khan |
| collection | DOAJ |
| description | The present study was the first comprehensive investigation of genetic mutation and expression levels of the p53 signaling genes in cutaneous melanoma through various genetic databases providing large datasets. The mutational landscape of p53 and its signaling genes was higher than expected, with TP53 followed by CDKN2A being the most mutated gene in cutaneous melanoma. Furthermore, the expression analysis showed that TP53 , MDM2 , CDKN2A , and TP53BP1 were overexpressed, while MDM4 and CDKN2B were under-expressed in cutaneous melanoma. Overall, TCGA data revealed that among all the other p53 signaling proteins, CDKN2A was significantly higher in both sun and non-sun-exposed healthy tissues than in melanoma. Likewise, MDM4 and TP53BP1 expressions were markedly greater in non-sun-exposed healthy tissues compared to other groups. However, CDKN2B expression was higher in the sun-exposed healthy tissues than in other tissues. In addition, various genes were expressed significantly differently among males and females. In addition, CDKN2A was highly expressed in the SK-MEL-30 skin cancer cell line, whereas, Immune cell type expression analysis revealed that the MDM4 was highly expressed in naïve B-cells. Furthermore, all six genes were significantly overexpressed in extraordinarily overweight or obese tumor tissues compared to healthy tissues. MDM2 expression and tumor stage were closely related. There were differences in gene expression across patient age groups and positive nodal status. TP53 showed a positive correlation with B cells, MDM2 with CD8+ T cells, macrophages and neutrophils, and MDM4 with neutrophils. CDKN2A/B had a non-significant correlation with all six types of immune cells. However, TP53BP1 was positively correlated with all five types of immune cells except B cells. Only TP53, MDM2 , and CDKN2A had a role in cutaneous melanoma-specific tumor immunity. All TP53 and its regulating genes may be predictive for prognosis. The results of the present study need to be validated through future screening, in vivo, and in vitro studies. |
| first_indexed | 2024-03-12T01:19:26Z |
| format | Article |
| id | doaj.art-4b4dcebd0d5c4bc9bf4e59b44d849741 |
| institution | Directory Open Access Journal |
| issn | 1176-9351 |
| language | English |
| last_indexed | 2024-03-12T01:19:26Z |
| publishDate | 2023-08-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Informatics |
| spelling | doaj.art-4b4dcebd0d5c4bc9bf4e59b44d8497412023-09-13T08:33:21ZengSAGE PublishingCancer Informatics1176-93512023-08-012210.1177/11769351231177267TP53 and its Regulatory Genes as Prognosis of Cutaneous MelanomaSafir Ullah Khan0Zahid Ullah1Hadia Shaukat2Shiza Unab3Saba Jannat4Waqar Ali5Amir Ali6Muhammad Irfan7Muhammad Fiaz Khan8Rodolfo Daniel Cervantes-Villagrana9Department of Cell Biology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, MexicoDepartment of Software Engineering, Abasyn University Peshawar, Peshawar, PakistanDepartment of Zoology, Women University of Swabi, Swabi, Khyber Pakhtunkhwa, PakistanDepartment of Zoology, University of Mianwali, Mianwali, PakistanDepartment of Zoology, Women University of Swabi, Swabi, Khyber Pakhtunkhwa, PakistanBiochemical and Biotechnological Sciences Università degli studi della Campania Luigi Vanvitelli, Caserta, Campania, ItalyNanosciences and Nanotechnology Program, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, MexicoDepartment of Zoology, Wildlife and Fisheries, Pir Mehr Ali Shah Arid Agriculture University Rawalpindi, Punjab, PakistanDepartment of Zoology, Hazara University, Mansehra, PakistanDepartment of Pharmacology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, MexicoThe present study was the first comprehensive investigation of genetic mutation and expression levels of the p53 signaling genes in cutaneous melanoma through various genetic databases providing large datasets. The mutational landscape of p53 and its signaling genes was higher than expected, with TP53 followed by CDKN2A being the most mutated gene in cutaneous melanoma. Furthermore, the expression analysis showed that TP53 , MDM2 , CDKN2A , and TP53BP1 were overexpressed, while MDM4 and CDKN2B were under-expressed in cutaneous melanoma. Overall, TCGA data revealed that among all the other p53 signaling proteins, CDKN2A was significantly higher in both sun and non-sun-exposed healthy tissues than in melanoma. Likewise, MDM4 and TP53BP1 expressions were markedly greater in non-sun-exposed healthy tissues compared to other groups. However, CDKN2B expression was higher in the sun-exposed healthy tissues than in other tissues. In addition, various genes were expressed significantly differently among males and females. In addition, CDKN2A was highly expressed in the SK-MEL-30 skin cancer cell line, whereas, Immune cell type expression analysis revealed that the MDM4 was highly expressed in naïve B-cells. Furthermore, all six genes were significantly overexpressed in extraordinarily overweight or obese tumor tissues compared to healthy tissues. MDM2 expression and tumor stage were closely related. There were differences in gene expression across patient age groups and positive nodal status. TP53 showed a positive correlation with B cells, MDM2 with CD8+ T cells, macrophages and neutrophils, and MDM4 with neutrophils. CDKN2A/B had a non-significant correlation with all six types of immune cells. However, TP53BP1 was positively correlated with all five types of immune cells except B cells. Only TP53, MDM2 , and CDKN2A had a role in cutaneous melanoma-specific tumor immunity. All TP53 and its regulating genes may be predictive for prognosis. The results of the present study need to be validated through future screening, in vivo, and in vitro studies.https://doi.org/10.1177/11769351231177267 |
| spellingShingle | Safir Ullah Khan Zahid Ullah Hadia Shaukat Shiza Unab Saba Jannat Waqar Ali Amir Ali Muhammad Irfan Muhammad Fiaz Khan Rodolfo Daniel Cervantes-Villagrana TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma Cancer Informatics |
| title | TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma |
| title_full | TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma |
| title_fullStr | TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma |
| title_full_unstemmed | TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma |
| title_short | TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma |
| title_sort | tp53 and its regulatory genes as prognosis of cutaneous melanoma |
| url | https://doi.org/10.1177/11769351231177267 |
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