Precisely, MTHFR could act as blockbuster biomarker for ipilimumab to melanoma of anti-CTLA-4 ontreatment (AUC = 0.9, P < 0.0001) and potential cancer biomarker for nivolumab to melanoma of anti-PD-1 ontreatment (AUC = 0.712, P = 0.006). The gene discussed is MTHFR; the disease is cancer.