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 followed by being the most mutated gene in cutaneous melanoma. Furthermore, the expression analysis showed , , , and were overexpressed, while and 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, was highly expressed in the SK-MEL-30 skin cancer cell line, whereas, Immune cell type expression analysis revealed that the 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. expression and tumor stage were closely related. There were differences in gene expression across patient age groups and positive nodal status. showed a positive correlation with B cells, with CD8+ cells, macrophages and neutrophils, and with neutrophils. had a non-significant correlation with all six types of immune cells. However, was positively correlated with all five types of immune cells except B cells. Only , and 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.