TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma

Safir Ullah Khan; Zahid Ullah; Hadia Shaukat; Sheeza Unab; Saba Jannat; Waqar Ali; Amir Ali; Muhammad Irfan; Muhammad Fiaz Khan; Rodolfo Daniel Cervantes-Villagrana

doi:10.1177/11769351231177267

TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma

Cancer Inform. 2023 Aug 31:22:11769351231177267. doi: 10.1177/11769351231177267. eCollection 2023.

Authors

Affiliations

¹ Department of Cell Biology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico.
² Department of Software Engineering, Abasyn University Peshawar, Peshawar, Pakistan.
³ Department of Zoology, Women University of Swabi, Swabi, Khyber Pakhtunkhwa, Pakistan.
⁴ Department of Zoology, University of Mianwali, Mianwali, Pakistan.
⁵ Biochemical and Biotechnological Sciences Università degli studi della Campania Luigi Vanvitelli, Caserta, Campania, Italy.
⁶ Nanosciences and Nanotechnology Program, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico.
⁷ Department of Zoology, Wildlife and Fisheries, Pir Mehr Ali Shah Arid Agriculture University Rawalpindi, Punjab, Pakistan.
⁸ Department of Zoology, Hazara University, Mansehra, Pakistan.
⁹ Department of Pharmacology, Center for Research and Advanced Studies, National Polytechnic Institute, Mexico City, Mexico.

Abstract

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.

Keywords: Mutations; cutaneous melanoma; expression; p53 signaling genes.