Underexpression of Specific Interferon Genes Is Associated with Poor Prognosis of Melanoma

Because the prognosis of melanoma is challenging and inaccurate when using current clinical approaches, clinicians are seeking more accurate molecular markers to improve risk models. Accordingly, we performed a survival analysis on 404 samples from The Cancer Genome Atlas (TCGA) cohort of skin cutaneous melanoma. Using our recently developed gene network model, we identified biological signatures that confidently predict the prognosis of melanoma (p-value < 10-5). Our model predicted 38 cases as low-risk and 54 cases as high-risk. The probability of surviving at least 5 years was 64% for low-risk and 14% for high-risk cases. In particular, we found that the overexpression of specific genes in the mitotic cell cycle pathway and the underexpression of specific genes in the interferon pathway are both associated with poor prognosis. We show that our predictive model assesses the risk more accurately than the traditional Clark staging method. Therefore, our model can help clinicians design treatment strategies more effectively. Furthermore, our findings shed light on the biology of melanoma and its prognosis. This is the first in vivo study that demonstrates the association between the interferon pathway and the prognosis of melanoma.