Minimally invasive multi-omics profiling – a powerful approach for disease diagnostics show-cased for coronary artery disease but equally applicable for cancer

Background: Cardiovascular diseases (CVD), a group of several conditions affecting the heart and blood vessel system, are the major cause of death worldwide. One example of these conditions is coronary artery disease (CAD) which causes a narrowing of blood vessels, typically by atherosclerotic plaque formation. This narrowing of coronary arteries (also called stenosis) and the resulting nutrient and oxygen shortage can damage the heart and can further lead to acute cardiac events such as a Myocardial Infarction. Up to now, coronary angiography (CA), which is an invasive cardiac catheterization method involving X-ray imaging, remains the state-of-the-art procedure to diagnose sclerotic lesions. However, about 40% of performed CAs reveal no significant abnormalities in coronary arteries. Therefore, this study aims at developing novel, minimally invasive multi-omics biomarkers for stenosis prediction and thereby reduce the given radiation exposure and invasiveness of CA.
Methods: The sample cohort underlying this study consist of whole blood, plasma and cell-free saliva collected from a total of 157 patients, which had undergone CA. 84 of these patients showed significant stenosis, which was defined as > 50% lumen narrowing in at least one coronary artery. We performed biomarker discovery studies with about 30-40 patients per experimental group and omics layer. The discovery on the 3 omics layers was conducted via A) genome-wide DNA methylation profiling from whole blood on Illumina EPIC microarrays, B) proteome-wide antibody profiling from plasma on in-house produced high density protein microarrays and C) small RNA sequencing from plasma- and cell-free saliva-derived extracellular vesicles.
Results: The current preliminary data showed a variety of statistically significant differences in DNA-methylation-, small RNA and autoantibody profiles between stenosis and non-stenosis patients.
Conclusion: Multi-omics profiling from liquid biopsies such as blood and saliva is a promising approach to diagnose and give insight into complex diseases such as CAD and cancer.