Hierarchical Clustering of Cutaneous Melanoma Based on Immunogenomic Profiling.
Hierarchical Clustering of Cutaneous Melanoma Based on Immunogenomic Profiling.
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DOI：
10.3389/fonc.2020.580029
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发表时间：
2020
影响因子：
4.7
通讯作者：
Ruan J
中科院分区：
文献类型：
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作者：
Yu J;Xie M;Ge S;Chai P;Zhou Y;Ruan J
皮肤黑色素瘤是一种高度异质性的侵袭性恶性肿瘤。已经进行了几项研究，以确定皮肤黑色素瘤亚型的基因组分析的基础上。然而，基于免疫相关基因评估的分类对皮肤黑色素瘤的临床意义有限。使用来自癌症基因组图谱（TCGA）的470个皮肤黑色素瘤样本，我们计算了每个样本中29个免疫相关基因集的富集水平，并将它们分层聚类到免疫高水平，基于ssGSEA评分，免疫系统分为三组，即免疫力（Immunity_H，n=323，68.7%）、免疫力中等（Immunity_M，n=135，28.7%）和免疫力低（Immunity_L，n=12，2.6%）。使用ESTIMATE算法计算基质评分（范围：-1，800.51-1，901.99），免疫评分（范围：-1，476.28-3，780.33），估计评分（范围：-2，618.28-5，098.14）和肿瘤纯度（范围：0.216-0.976），与免疫亚型显著相关（Kruskal-Wallis检验，P < 0.001）。Immunity_H组HLA和免疫检查点基因的表达水平更高（Kruskal-Wallis检验，P < 0.05）。Immunity_H组的幼稚B细胞、静息树突状细胞、M1巨噬细胞、静息NK细胞、浆细胞、CD 4记忆激活T细胞、CD 8 T细胞、滤泡辅助性T细胞和调节性T细胞水平最高，Immunity_L组的总体生存率更高。Immunity_H组中识别的GO术语主要与免疫相关。总之，免疫特征相关的皮肤黑色素瘤亚型在皮肤黑色素瘤预后分层中发挥作用。免疫特征相关皮肤黑色素瘤亚型的构建预测了可能的患者结果，并提供了可能的免疫治疗候选药物。
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.
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