Cutaneous melanoma is one of the most aggressive cancers characterized by increasing incidence and mortality. In recent years, the emergence of immunotherapy has greatly raised the survival rate of patients suffering from cutaneous melanoma, yet some sufferers remain to have poor outcomes after treatment mainly due to the tumor microenvironment (TME). In this study, cutaneous melanoma–associated TME was systematically analyzed using the ESTIMATE algorithm based on the gene transcriptome data obtained from the TCGA database. Totally, 471 patients were included and 553 TME-related genes were screened. Afterwards, a 3-gene signature–based model (CLEC4A, GBP4, KIR2DL4) was constructed via univariate Cox, LASSO, and multivariate Cox regression analyses. To validate the validity of this model, ROC analysis was conducted, and the model was further validated to be an independent prognostic biomarker through univariate and multivariate regression analyses. Finally, the three genes in the model were studied by GSEA and GSVA for their biological significance. We found that the three genes could promote cancer immune response predominantly through affecting immune-related pathways such as antigen processing and presentation, and they may help tumor cells in escaping from surveillance of the immune system when their expression levels were decreased. Additionally, we as well discovered that the expression of the three genes was significantly and positively correlated with the infiltration of related immune cells, but negatively associated with tumor purity. Overall, this study comprehensively analyzed the TME of cutaneous melanoma, identified related biomarkers, and discovered their association with immune system.

皮肤黑素瘤是最具侵袭性的癌症之一，其特征是发病率和死亡率增加。近年来，免疫疗法的出现极大地提高了皮肤黑色素瘤患者的存活率，但是一些患者在治疗后仍然主要由于肿瘤微环境（TME）而效果欠佳。在这项研究中，基于从TCGA数据库获得的基因转录组数据，使用ESTIMATE算法对皮肤黑色素瘤相关的TME进行了系统分析。总共纳入471位患者，并筛选了553个TME相关基因。之后，通过单变量Cox，LASSO和多变量Cox回归分析，构建了基于3基因签名的模型（CLEC4A，GBP4，KIR2DL4）。为了验证该模型的有效性，进行了ROC分析，通过单因素和多元回归分析，该模型被进一步验证为独立的预后生物标志物。最后，GSEA和GSVA研究了模型中的三个基因的生物学意义。我们发现这三个基因主要通过影响免疫相关途径（如抗原加工和呈递）来促进癌症的免疫反应，并且当它们的表达水平降低时，它们可以帮助肿瘤细胞逃避免疫系统的监视。另外，我们还发现这三个基因的表达与相关免疫细胞的浸润显着正相关，而与肿瘤纯度负相关。总体而言，这项研究全面分析了皮肤黑色素瘤的TME，确定了相关的生物标志物，