Gene Expression of A375 Cells After Fluvastatin Treatment

Despite advances in melanoma treatment, more than 70% of patients with distant metastasis die within 5 years. Proactive treatment of early melanoma to prevent metastasis could save lives and reduce overall healthcare costs. Currently, there are no treatments specifically designed to prevent early melanoma from progressing to metastasis. We used the Connectivity Map (cMap) to conduct an in silico drug screen and identified HMGCR inhibitors (statins) as a drug class that might prevent melanoma metastasis. To confirm the in vitro effect of statins, RNA-sequencing was completed on A375 cells after treatment with fluvastatin to describe changes in the melanoma transcriptome. Statins induced differential expression in genes associated with metastasis and used in commercially available prognostic tests for melanoma metastasis. Overall design: We used RNA-sequencing to measure gene expression of A375 melanoma cells before and after treatment with fluvastatin. The A375 cell line was specifically chosen since it has moderate metastatic potential and has been used in previous mechanistic studies of statins. Fluvastatin was chosen because of its lipophilicity (allowing extrahepatic distribution), benign side effect profile, and excellent bioavailability. We found 2615 differentially expressed genes