Challenges in developing DNA and RNA biomarkers of inflammation

Abstract

Inflammation is now a proven cause of human diseases such as cancer and cardiovascular disease. One potential link between inflammation and disease involves secretion of reactive chemical species by immune cells, with chronic damage to host epithelial cells leading to disease. This suggests pathophysiologically that DNA and RNA damage products are candidate biomarkers of inflammation, both for mechanistic understanding of the process and for risk assessment. Of the current approaches to quantifying DNA damage products, mass spectrometry-based methods provide the most rigorous quantification needed for biomarker development, while antibody-based approaches provide the most practical way to implement biomarkers in a clinical setting. Nonetheless, all approaches are biased by adventitious formation of DNA and RNA damage products during sample processing. Recent studies of tissue-derived DNA biomarkers in mouse models of inflammation reveal significant changes only in DNA adducts derived from lipid peroxidation. These and other observations raise the question of the most appropriate sampling compartment for DNA biomarker studies and highlight the emerging role of lipid damage in inflammation.