Li Xia, Cai Yunpeng
Research Center for Biomedical Information Technology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, P.R. China.
Aging (Albany NY). 2019 Jul 18;11(14):5081-5107. doi: 10.18632/aging.102099.
Melanoma is the most dangerous type of skin cancer and has highly heterogeneous features. Despite progress in melanoma classification, interpatient heterogeneity remains difficult to predict, especially in terms of long-term survival. Here, based on mRNA-seq, miRNA-seq and DNA methylation data from 447 cutaneous melanoma patients in the Cancer Genome Atlas, we performed integrative and single-dataset clustering analyses. A novel group of patients was identified, including 301 with better, 55 with poorer and 91 with intermediate prognoses. Immune genes were upregulated in the better prognostic group, and higher immune scores (representing a greater extent of immune cell infiltration into tumor tissues) were associated with better prognoses. Higher expression of 115 genes was determined to predict better outcomes. The better prognostic group also exhibited DNA hypomethylation, and immune pathways were enriched among the hypomethylated genes. Using exome-seq data from the same patients, we observed that the better prognostic group harbored the highest number of mutations. The mutational signature in the better prognostic group was associated with ultraviolet light exposure. These integrated investigations have potential therapeutic significance, as they clarify the molecular heterogeneity of cutaneous melanoma and enhance its classification.
黑色素瘤是最危险的皮肤癌类型，具有高度异质性特征。尽管黑色素瘤分类取得了进展，但患者间的异质性仍然难以预测，尤其是在长期生存方面。在此，基于癌症基因组图谱中447例皮肤黑色素瘤患者的mRNA测序、miRNA测序和DNA甲基化数据，我们进行了综合和单数据集聚类分析。识别出一组新的患者群体，包括预后较好的301例、预后较差的55例和预后中等的91例。免疫基因在预后较好的组中上调，较高的免疫评分（代表免疫细胞浸润肿瘤组织的程度更高）与较好的预后相关。确定115个基因的高表达可预测更好的结果。预后较好的组还表现出DNA低甲基化，免疫途径在低甲基化基因中富集。利用同一患者的外显子组测序数据，我们观察到预后较好的组中突变数量最多。预后较好的组中的突变特征与紫外线暴露有关。这些综合研究具有潜在的治疗意义，因为它们阐明了皮肤黑色素瘤的分子异质性并改进了其分类。
