State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510064, China.
Aging (Albany NY). 2020 Oct 26;12(20):20684-20701. doi: 10.18632/aging.103974.
Molecular pathways regulating the initiation and development of melanoma are potential therapeutic targets for this aggressive skin cancer. Therefore, transcriptome profiles of cutaneous melanoma were obtained from a public database and used to systematically evaluate cancer hallmark pathways enriched in melanoma. Finally, the unfolded protein response pathway was screened out, and the unfolded protein response-related genes were used to develop a robust biomarker that can predict the prognosis of melanoma, especially for younger, metastatic and high Clark level patients. This biomarker was further validated in two other independent datasets. In addition, melanoma patients were divided into high- and low-risk subgroups by applying a risk score system. The high-risk group exhibited higher immune infiltration and higher expression of N6-methyladenosine RNA methylation regulators, and had significantly shorter survival times than the low-risk subgroup. Gene Set Enrichment Analysis revealed that, among the enriched genes, gene sets involved in immune response and the extracellular matrix receptor interaction were significantly activated in the high-risk group. Our findings thus provide a new clinical application for prognostic prediction as well as potential targets for treatment of melanoma.
调控黑色素瘤发生和发展的分子通路是治疗这种侵袭性皮肤癌的潜在靶点。因此，我们从公共数据库中获取了皮肤黑色素瘤的转录组图谱，并用于系统地评估黑色素瘤中富集的癌症标志性通路。最终筛选出未折叠蛋白反应通路，并利用未折叠蛋白反应相关基因开发了一种稳健的生物标志物，可预测黑色素瘤的预后，尤其是对年轻、转移性和高 Clark 分级的患者。该生物标志物在另外两个独立数据集得到了进一步验证。此外，我们还通过应用风险评分系统将黑色素瘤患者分为高风险组和低风险组。高风险组表现出更高的免疫浸润和 N6-甲基腺苷 RNA 甲基化调节因子的更高表达，并且与低风险组相比，其生存时间明显缩短。基因集富集分析显示，在富集的基因中，高风险组中与免疫反应和细胞外基质受体相互作用相关的基因集显著激活。因此，我们的研究结果为黑色素瘤的预后预测提供了新的临床应用，也为治疗提供了潜在的靶点。
