Pre-treatment DNA methylome and transcriptome profiles correlate with melanoma response to anti-PD1 immunotherapy.

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Tác giả: Suzan Almomani, Basharat Bhat, Aniruddha Chatterjee, Bozena Cybulska-Stopa, Michael R Eccles, Gregory Gimenez, Agnieszka Harazin-Lechowska, Sultana Mehbuba Hossain, Christopher Jackson, Gregory T Jones, Magdalena Ratajska, Euan Rodger, Janusz Ryś, Mathew Shuen, Peter Stockwell, Robert Weeks

Ngôn ngữ: eng

Ký hiệu phân loại: 598.34 *Ciconiiformes

Thông tin xuất bản: Ireland : Cancer letters , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 713860

 Successful immune checkpoint inhibitor (ICI) therapy occurs in only a fraction of melanoma patients, and yet all patients are susceptible to potentially serious ICI-related side-effects. No current biomarkers robustly predict ICI treatment response in melanoma patients. In this study we sought to identify methylome and transcriptome markers which have the potential to predict immunotherapy response in melanoma patients ahead of treatment with anti-PD1 ICI monotherapy. Using Infinium MethylationEPIC microarrays, we analysed DNA methylation profiles of >
 850,000 CpG sites in pre-treatment melanoma tissues from patients administered anti-PD-1 monotherapy as first-line treatment. In addition, we analysed transcriptomes using RNA-seq. DNA methylation and gene expression data were then statistically compared to patient response to anti-PD1 therapy. We identified 2,579 DNA hypomethylation and hypermethylation alterations correlating with melanoma response to anti-PD1 therapy. An integrative analysis of DNA methylomes and transcriptomes identified a subset of 35 loci, 13 of which were significantly differentially methylated in both initial discovery and external validation datasets. Functional enrichment analysis of hypomethylated sites (p-value <
  0.05) in non-responders was associated with "Formation of the cornified envelope", "Regulation of epithelial cell proliferation", and "Purine-containing compound metabolic process". We have identified novel integrated DNA methylation and gene expression markers, which correlate with anti-PD1 treatment response in melanoma patients. These findings suggest a relationship between tumour-associated genomic DNA methylation, gene expression patterns, and anti-PD1 ICI immunotherapy response in melanoma patients.
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