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N6-methyladenosine RNA Methylation Correlates with Immune Microenvironment and Immunotherapy Response of Melanoma.
Wang, Gaofeng; Zeng, Dongqiang; Sweren, Evan; Miao, Yong; Chen, Ruosi; Chen, Junjun; Wang, Jin; Liao, Wangjun; Hu, Zhiqi; Kang, Sewon; Garza, Luis A.
Afiliación
  • Wang G; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Zeng D; Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Sweren E; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Miao Y; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Chen R; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Chen J; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Wang J; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Liao W; Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Hu Z; Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Kang S; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • Garza LA; Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Cell Biology, Johns Hopkins University, Baltimore, Maryland, USA; Department of Oncology, Johns Hopkins University, Baltimore, Maryland, USA. Electronic address: LAG@jhmi.edu.
J Invest Dermatol ; 143(8): 1579-1590.e5, 2023 08.
Article en En | MEDLINE | ID: mdl-36842525
RNA methylation normally inhibits the self-recognition and immunogenicity of RNA. As such, it is likely an important inhibitor of cancer immune recognition in the tumor microenvironment, but how N6-methyladenosine (m6A) affects prognosis and treatment response remains unknown. In eight independent melanoma cohorts (1,564 patients), the modification patterns of 21 m6A gene signatures were systematically correlated with the immune cell infiltration of melanoma tumor microenvironment. m6A modification patterns for each patient were quantified using the principal component analysis method, yielding an m6Ascore that reflects the abundance of m6A RNA modifications. Two different m6A modification patterns were observed in patients with melanoma, separated into high and low m6Ascores that correlated with survival and treatment response. Low m6Ascores were characterized by an immune-inflamed phenotype, with 61.1% 5-year survival. High m6Ascores were characterized by an immune-excluded phenotype, with 52.2% 5-year survival. Importantly, lower m6Ascores correlated with more sensitive anti-PD-1 and anti-CTLA4 treatment responses, with 90% of patients with low m6Ascore responding, whereas 10% of those with high m6Ascore nonresponding (in cohort GSE63557). At single-cell and spatial transcriptome resolution, m6Ascore reflects melanoma malignant progression, immune exhaustion, and resistance to immune checkpoint blockade therapy. Hence, the m6Ascore correlates to an important facet of tumor immune escape as a tool for personalized medicine to guide immunotherapy in patients with melanoma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Melanoma Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos