Randerson-Moor, J., Davies, J., Harland, M. et al. (10 more authors) (2024) Systemic inflammation, the peripheral blood transcriptome and primary melanoma. Journal of Investigative Dermatology. ISSN 0022-202X
Abstract
Peripheral blood transcriptomes from 383 newly-diagnosed melanoma patients were subjected to differential gene expression analysis. The hypotheses were that impaired systemic immunity is associated with poorer prognosis (thicker tumors and fewer tumor infiltrating lymphocytes (TILs)) and evidence of systemic inflammation (high-sensitivity C-reactive protein (hsCRP) and fibrinogen levels). Higher fibrinogen levels were associated with thicker primaries. In single gene analysis hsCRP levels were significantly associated with higher blood CD274 expression, (coding for PD-L1), but each was independently prognostic, with hsCRP associated with increased mortality, and higher CD274 protective, independent of age. Pathway analysis identified downregulation of immune cell signalling pathways in the blood of people with thicker tumors and notable upregulation of STAT1 in people with brisk TILs. Transcriptomic data provided evidence for increased NFB signalling with higher inflammatory markers but with reduction in expression of HLA class II molecules and higher CD274 suggesting that aberrant systemic inflammation is a significant mediator of reduced immune function in melanoma. In summary, transcriptomic data revealed evidence of reduced immune function in patients with thicker tumors and fewer TILs, at diagnosis. Inflammatory markers were associated with thicker primaries and independently with death from melanoma suggesting that systemic inflammation contributes to that reduced immune function.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | CRP, CD274, PD-L1, TILs, Breslow |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Medical Research (LIMR) > Division of Haematology and Immunology |
Depositing User: | Symplectic Publications |
Date Deposited: | 03 Apr 2024 09:23 |
Last Modified: | 16 Apr 2024 11:44 |
Status: | Published online |
Publisher: | Elsevier |
Identification Number: | https://doi.org/10.1016/j.jid.2024.02.034 |
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Filename: JID-2023-0578-text.pdf