Discovery and Validation of a SIT1-Related Prognostic Signature Associated with Immune Infiltration in Cutaneous Melanoma

Signaling threshold regulating transmembrane adaptor 1 (SIT1) encodes a disulfide-linked homodimeric lymphocyte-specific glycoprotein involved in immune cell activation. However, the relationship between SIT1 and the prognosis of skin cutaneous melanoma (SKCM) and tumor-infiltrating lymphocytes remains elusive. Here, we first compared the differences in SIT1 expression levels between SKCM tissues and adjacent normal tissues. Next, we found that the immune cell infiltration levels and signature pattern of immune infiltration were positively associated with the SIT1 gene mRNA levels. TCGA_SKCM RNA-seq data unveiled that the SIT1 upregulated several immune-associated signaling pathways in GSEA analysis. The high expression of SIT1 was closely related to improved survival in patients with SKCM. A pathway enrichment analysis of SIT1-associated immunomodulators indicated the involvement of the NF-κB signaling pathways. Based on SIT1-associated immunomodulators, we built a 13-gene signature by LASSO Cox regression which served as an independent prognostic factor for the survival of melanoma patients. By using the signature risk score, we achieved a good prediction result for the immunotherapy response and survival of SKCM patients. Our findings provided evidence for SIT1’s implication in tumor immunity and survival of SKCM patients. The nominated immune signature is a promising predictive model for prognosis and immunotherapy sensitivity in SKCM patients.