In this signature, low expression levels of ICOS (HR = 0.48, 95% CI = 0.29–0.80, p-value = 0.007), ISG20 (HR = 0.44, 95% CI = 0.26–0.74, p-value = 0.010) and high expression levels of ANGPTL4 (HR = 2.08, 95% CI = 1.20–3.59, p-value = 0.004), SBDS (HR = 1.96, 95% CI = 1.18–3.26, p-value = 0.015), and LTBR (HR = 1.73, 95% CI = 1.04–2.88, p-value = 0.045) were risk factors for CSCC prognosis, suggesting poor OS (Figures 3A–E). This evidence concerns the gene ISG20 and skin squamous cell carcinoma.