No abstract

Malignant melanoma is an extremely malignant tumor with a high mortality rate and an increasing incidence with a high mutation load. The frequency of mutations in the TERT promoter exceeds the frequency of any known noncoding mutations in melanoma. A growing number of recent studies suggest that the most common mutations in the TERT promoter (ATG start site −124C>T and −146C>T) are associated with increased TERT mRNA expression, telomerase activity, telomere length, and poor prognosis. Recently, it has been shown that TERT promoter mutations are more correlated with the occurrence, development, invasion, and metastasis of melanoma, as well as emerging approaches such as the therapeutic potential of chemical inhibition of TERT promoter mutations, direct telomerase inhibitors, combined targeted therapy, and immunotherapies. In this review, we describe the latest advances in the role of TERT promoter mutations and telomerase in promoting the occurrence, development, and poor prognosis of melanoma and discuss the clinical significance of the TERT promoter and telomerase in the treatment of melanoma.

Background: There exists a lack of effective tools predicting prognosis for cutaneous melanoma patients. Glycolysis plays an essential role in the carcinogenesis process. Objective: : We intended to construct a new prognosis model for cutaneous melanoma. Method: Based on the data from TCGA database, we conducted univariate Cox regression analysis and identified prognostic glycolysis-related genes (GRGs). Meanwhile, GSE15605 dataset was used to identify differentially expressed genes (DEGs). The intersection of prognostic GRGs and DEGs was extracted for the subsequent multivariate Cox regression analysis. Results: A prognostic signature containing ten GRGs was built, and the TCGA cohort was classified into high and low risk subgroups based on risk score of each patient. K-M analysis manifested that the overall survival of high-risk group was statistically worse than that of low-risk group. Further study indicated that the risk-score could be used as an independent prognostic factor which effectively predicted the clinical prognosis in patients with different age, gender and stage. GO and KEGG enrichment analysis showed DEGs between high and low risk groups were enriched in immune-related functions and pathways. In addition, a significant difference existed between high and low risk groups in infiltration pattern of immune cell and expression levels of inhibitory immune checkpoint genes. Conclusion: A new glycolysis-related gene signature was established for identifying cutaneous melanoma patients with poor prognosis and formulating individualized treatment for them.