DNA methylation variations of DNA damage response correlate survival and local immune status in melanomas

IF 3.1 4区 医学 Q3 IMMUNOLOGY Immunity, Inflammation and Disease Pub Date : 2024-09-10 DOI:10.1002/iid3.1331
Min Wang, Xiao-dong Zhang, Han-qing Yang, Yang Li, Wen-mei Chen, An-an Yin
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Abstract

Aim

We aimed to explore the impact of DNA methylation alterations on the DNA damage response (DDR) in melanoma prognosis and immunity.

Material & methods

Different melanoma cohorts with molecular and clinical data were included.

Results

Hierarchical clustering utilizing different combinations of DDR-relevant CpGs yielded distinct melanoma subtypes, which were characteristic of different prognoses, transcriptional function profiles of DDR, and immunity and immunotherapy responses but were associated with similar tumor mutation burdens. We then constructed and validated a clinically applicable 4-CpG risk-score signature for predicting survival and immunotherapy response.

Conclusion

Our study describes the close interrelationship among DNA methylation, DDR machinery, local tumor immune status, melanoma prognosis, and immunotherapy response.

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DNA 损伤反应的 DNA 甲基化变异与黑色素瘤的存活率和局部免疫状态有关
目的 我们旨在探讨DNA甲基化改变对黑色素瘤预后和免疫中DNA损伤应答(DDR)的影响。 材料& 方法 纳入了不同的黑色素瘤队列的分子和临床数据。 结果 利用与 DDR 相关的 CpGs 的不同组合进行层次聚类,得出了不同的黑色素瘤亚型,这些亚型具有不同的预后、DDR 的转录功能特征以及免疫和免疫治疗反应,但与相似的肿瘤突变负荷相关。然后,我们构建并验证了适用于临床的 4-CpG 风险评分特征,用于预测生存率和免疫治疗反应。 结论 我们的研究描述了 DNA 甲基化、DDR 机制、局部肿瘤免疫状态、黑色素瘤预后和免疫治疗反应之间的密切相互关系。
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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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