Background: The tumor microenvironment (TME) is critical in the progression and metastasis of skin cutaneous melanoma (SKCM). Differences in tumor-infiltrating immune cells (TICs) and their gene expression have been linked to cancer prognosis. Given that immunotherapy can be effective against SKCM, we aimed to identify key genes that regulate the immunological state of the TME in SKCM.
Methods: Data from 471 SKCM patients in the The Cancer Genome Atlas were analyzed using ESTIMATE algorithms to generate an ImmuneScore, StromalScore, and EstimateScore for each patient. Patients were classified into low- or high-score groups based on median values, then compared in order to identify differentially expressed genes (DEGs). Then a protein-protein interaction (PPI) network was developed, and a prognostic model was created using uni- and multivariate Cox regression as well as the least absolute shrinkage and selection operator (LASSO). Key DEGs were identified using the web-based tool GEPIA. Profiles of TIC subpopulations in each patient were analyzed using CIBORSORT, and possible correlations between key DEG expression and TICs were explored. Levels of CCL8 were determined in SKCM and normal skin tissue using immunohistochemistry.
Results: Two scores correlated positively with the prognosis of SKCM patients. Comparison of the low- and high-score groups revealed 1684 up-regulated and 18 down-regulated DEGs, all of which were enriched in immune-related functions. The prognostic model identified CCL8 as a key gene, which CIBERSORT found to correlate with M1 macrophages. Immunohistochemistry revealed strong expression in SKCM tissue, but failed to detect the protein in normal skin tissue.
Conclusions: CCL8 is a potential prognostic marker for SKCM, and it may become an effective target for melanoma in which M1 macrophages play an important role.