黑色素瘤
免疫疗法
癌症研究
转移性黑色素瘤
免疫系统
转移
生物
血管生成
细胞
下调和上调
癌症
医学
免疫学
内科学
基因
遗传学
生物化学
作者
Haitao Xiang,Rongkui Luo,Yunzhi Wang,Bing Yang,Sha Xu,Wen-Ching Huang,Shaoshuai Tang,Rundong Fang,Lingli Chen,Na Zhu,Zixiang Yu,Akesu Sujie,Chuan‐Yuan Wei,Xu Chen,Yuhong Zhou,Jianying Gu,Jian‐Yuan Zhao,Yingyong Hou,Chen Ding
标识
DOI:10.1038/s41421-024-00688-7
摘要
Abstract Melanoma is one of the most prevalent skin cancers, with high metastatic rates and poor prognosis. Understanding its molecular pathogenesis is crucial for improving its diagnosis and treatment. Integrated analysis of multi-omics data from 207 treatment-naïve melanomas (primary-cutaneous-melanomas (CM, n = 28), primary-acral-melanomas (AM, n = 81), primary-mucosal-melanomas (MM, n = 28), metastatic-melanomas ( n = 27), and nevi ( n = 43)) provides insights into melanoma biology. Multivariate analysis reveals that PRKDC amplification is a prognostic molecule for melanomas. Further proteogenomic analysis combined with functional experiments reveals that the cis -effect of PRKDC amplification may lead to tumor proliferation through the activation of DNA repair and folate metabolism pathways. Proteome-based stratification of primary melanomas defines three prognosis-related subtypes, namely, the ECM subtype, angiogenesis subtype (with a high metastasis rate), and cell proliferation subtype, which provides an essential framework for the utilization of specific targeted therapies for particular melanoma subtypes. The immune classification identifies three immune subtypes. Further analysis combined with an independent anti-PD-1 treatment cohort reveals that upregulation of the MAPK7-NFKB signaling pathway may facilitate T-cell recruitment and increase the sensitivity of patients to immunotherapy. In contrast, PRKDC may reduce the sensitivity of melanoma patients to immunotherapy by promoting DNA repair in melanoma cells. These results emphasize the clinical value of multi-omics data and have the potential to improve the understanding of melanoma treatment.
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