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Systemic Inflammation, the Peripheral Blood Transcriptome, and Primary Melanoma
Juliette Randerson-Moor1, John Davies2, Mark Harland1
1Division of Haematology and Immunology, Leeds Institute of Medical Research (LIMR), School of Medicine, University of Leeds, Leeds, United Kingdom.
The Journal of Investigative Dermatology
|April 7, 2024
Summary
Systemic inflammation in melanoma patients is linked to poorer prognosis and reduced immune function, particularly in those with thicker tumors. Inflammatory markers like CRP and fibrinogen correlate with tumor thickness and mortality risk.
Area of Science:
- Immunology
- Oncology
- Genomics
Background:
- Systemic immunity and inflammation may impact melanoma prognosis.
- Understanding these systemic factors is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the association between peripheral blood transcriptomes, systemic inflammation, and clinical outcomes in newly diagnosed melanoma patients.
- To explore the relationship between inflammatory markers, tumor characteristics, and immune cell infiltration.
Main Methods:
- Differential gene expression analysis of peripheral blood transcriptomes from 383 melanoma patients.
- Correlation analysis of inflammatory markers (high-sensitivity CRP, fibrinogen) with tumor characteristics and gene expression.
- Pathway analysis to identify dysregulated signaling in relation to tumor-infiltrating lymphocytes and inflammation.
Main Results:
- Higher fibrinogen levels correlated with thicker primary tumors.
- High-sensitivity CRP was associated with increased mortality and higher CD274 (PD-L1) expression, while CD274 expression was protective.
- Transcriptomic analysis revealed downregulated immune cell signaling in patients with thicker tumors and STAT1 upregulation in those with brisk tumor-infiltrating lymphocytes.
- Increased NF-kB signaling and reduced HLA class II expression were observed with higher inflammatory markers, suggesting impaired immune function.
Conclusions:
- Peripheral blood transcriptomic data indicate reduced immune function in melanoma patients with thicker tumors and fewer tumor-infiltrating lymphocytes.
- Systemic inflammatory markers are associated with thicker tumors and independently predict melanoma mortality.
- Aberrant systemic inflammation appears to mediate reduced immune function in melanoma, highlighting its role in disease progression.
