9-Gene Signature Correlated With CD8(+) T Cell Infiltration Activated by IFN-γ: A Biomarker of Immune Checkpoint Therapy Response in Melanoma

PURPOSE: To identify CD8(+) T cell-related factors and the co-expression network in melanoma and illustrate the interactions among CD8(+) T cell-related genes in the melanoma tumor microenvironment. METHOD: We obtained melanoma and paracancerous tissue mRNA matrices from TCGA-SKCM and GSE65904. The CIBERSORT algorithm was used to assess CD8(+) T cell proportions, and the “estimate” package was used to assess melanoma tumor microenvironment purity. Weighted gene co-expression network analysis was used to identify the most related co-expression modules in TCGA-SKCM and GSE65904. Subsequently, a co-expression network was built based on the joint results in the two cohorts. Subsequently, we identified the core genes of the two most relevant modules of CD8(+)T lymphocytes according to the module correlation, and constructed the signature using ssGSEA. Later, we compared the signature with the existing classical pathways and gene sets, and confirmed the important prognostic significance of the signature in this paper. RESULTS: Nine co-expressed genes were identified as CD8(+) T cell-related genes enriched in the cellular response to interferon−gamma process and antigen processing and presentation of peptide antigen. In the low expression level group, inflammation and immune responses were weaker. Single-cell sequencing and immunohistochemistry indicated that these nine genes were highly expressed in CD8(+) T cells group. CONCLUSION: We identified nine-gene signature, and the signature is considered as the biomarker for T lymphocyte response and clinical response to immune checkpoint inhibitors for melanoma