Abstract
Cutaneous melanoma is an aggressive malignancy with high heterogeneity. Several studies have been performed to identify cutaneous melanoma subtypes based on genomic profiling. However, few classifications based on assessments of immune-associated genes have limited clinical implications for cutaneous melanoma. Using 470 cutaneous melanoma samples from The Cancer Genome Atlas (TCGA), we calculated the enrichment levels of 29 immune-associated gene sets in each sample and hierarchically clustered them into Immunity High (Immunity_H, n=323, 68.7%), Immunity Medium (Immunity_M, n=135, 28.7%), and Immunity Low (Immunity_L, n=12, 2.6%) based on the ssGSEA score. The ESTIMATE algorithm was used to calculate stromal scores (range: -1,800.51–1,901.99), immune scores (range: -1,476.28–3,780.33), estimate scores (range: -2,618.28–5,098.14) and tumor purity (range: 0.216–0.976) and they were significantly correlated with immune subtypes (Kruskal–Wallis test, P < 0.001). The Immunity_H group tended to have higher expression levels of HLA and immune checkpoint genes (Kruskal–Wallis test, P < 0.05). The Immunity_H group had the highest level of naïve B cells, resting dendritic cells, M1 macrophages, resting NK cells, plasma cells, CD4 memory activated T cells, CD8 T cells, follicular helper T cells and regulatory T cells, and the Immunity_L group had better overall survival. The GO terms identified in the Immunity_H group were mainly immune related. In conclusion, immune signature-associated cutaneous melanoma subtypes play a role in cutaneous melanoma prognosis stratification. The construction of immune signature-associated cutaneous melanoma subtypes predicted possible patient outcomes and provided possible immunotherapy candidates.
Highlights
Cutaneous melanoma is one of the most aggressive types of cancer due to an elevated degree of heterogeneity in the aspects of clinical presentation, histopathological presentation and genomic profiles [1]
Cutaneous melanoma patients’ stromal scores, immune scores, estimate scores, and tumor purity data are shown in Table S1
We found that the stromal scores, immune scores and estimate scores were significantly high in the Immunity_H group and significantly low in the Immunity_L group (Kruskal–Wallis test, P < 0.001) (Figures 2A–C), which suggested that these scores were meaningfully correlated with cutaneous melanoma
Summary
Cutaneous melanoma is one of the most aggressive types of cancer due to an elevated degree of heterogeneity in the aspects of clinical presentation, histopathological presentation and genomic profiles [1]. Nie RC et al developed an immunoscore based on eight immune subsets (naïve B cells, memory B cells, eosinophils, follicular helper T cells, regulatory T cells, M0 macrophages, plasma cells, and gdT cells), and cutaneous melanoma patients were divided into a high immunoscore group and a low immunoscore group to predict the anti-PD1 response [5]. These efforts indicate the importance of classifying cutaneous melanoma for diagnosis and treatment
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