Transcriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma

Although the abnormal expression of members of the E2F family has been reported to participate in carcinogenesis in many human types of cancer, the bioinformatics role of the E2F family in melanoma is unknown. This research was designed to detect the expression, methylation, prognostic value and potential effects of the E2F family in melanoma. We investigated E2F family mRNA expression from the Oncomine and GEPIA databases and their methylation status in the MethHC database. Meanwhile, we detected the relative E2F family expression levels by qPCR and immunohistochemistry. Kaplan-Meier Plotter was used to draw survival analysis charts, and gene functional enrichment analyses were applied through cBioPortal database analysis. E2F1/2/3/4/5/6 mRNA and proteins were clearly upregulated in cutaneous melanoma patients, and high expression levels of E2F1/2/3/6 were statistically related to high methylation levels. Increased mRNA expression of E2F1/2/3/6 was related to lower overall survival rates (OS) and disease-free survival (DFS) in cutaneous melanoma cases. Meanwhile, E2F1/2/3/6 carried out these effects through regulating multiple signaling pathways, including the MAPK, PI3K-Akt and p53 signaling pathways. Taking together, our findings suggest that E2F1/2/3/6 could act as potential targets for precision therapy in cutaneous melanoma patients.