Methylation analysis highlights novel prognostic criteria in human-metastasized melanoma

Melanoma accounts for 90% of the deaths associated with cutaneous neoplasms, and the 5-year survival rate of patients with the advanced stage is about 20%. Many mechanisms are involved in melanoma progression, but dynamic epigenetic changes are likely to be critical contributors, especially for DNA methylation. However, we know little about the methylation events involved in melanoma lymph node metastasis (LNM), a deficit that is of particular concern because it has a growing incidence and mortality. To identify DNA methylated-associated changes involved in the formation of metastatic melanoma, we explored the different methylated genes (DMGs) between primary and LNM melanoma by Illumina Human Methylation 450 K BeadArray GSE44661. By integrating DNA methylation and messenger RNA expression data from The Cancer Genome Atlas database, we identified these DNA methylation biomarkers. Pathway analysis highlighted these DMGs, which were closely related to the carcinogenesis of melanoma, such as cell cycle regulation and RNA transcription process. Furthermore, according to the univariate and multivariate Cox regression analysis, we constructed a four-DMG prognostic signature model, which could precisely predict the outcome of melanoma in a more exact way. In summary, this four-DMG based risk score model successfully predicts the survival of melanoma. It is independent of other clinical characteristics and is good for prognosis prediction.