Abstract
BACKGROUND: Biomarker analyses are an integral part of cancer research. Despite the intense efforts to identify and characterize biomarkers in patients with cancer, little is known regarding the natural variation of biomarkers in healthy populations. Here we conducted a clinical study to evaluate the natural variability of biomarkers over time in healthy participants. METHODS: The angiome multiplex array, a panel of 25 circulating protein biomarkers, was assessed in 28 healthy participants across eight timepoints over the span of 60 days. We utilized the intraclass correlation coefficient (ICC) to quantify the reliability of the biomarkers. Adjusted ICC values were calculated under the framework of a linear mixed-effects model, taking into consideration age, sex, body mass index, fasting status, and sampling factors. RESULTS: ICC was calculated to determine the reliability of each biomarker. Hepatocyte growth factor was the most stable marker (ICC = 0.973), while platelet-derived growth factor (PDGF)-BB was the most variable marker (ICC = 0.167). In total, ICC analyses revealed that 22 out of 25 measured biomarkers display good (≥0.4) to excellent (>0.75) ICC values. Three markers (PDGF-BB, TGFβ1, PDGF-AA) had ICC values <0.4. Greater age was associated with higher IL6 (P = 0.0114). Higher body mass index was associated with higher levels of IL6 (P = 0.0003) and VEGF-R3 (P = 0.0045). CONCLUSIONS: Of the 25 protein biomarkers measured over this short time period, 22 markers were found to have good or excellent ICC values, providing additional validation for this biomarker assay. IMPACT: These data further support the validation of the angiome biomarker assay and its application as an integrated biomarker in clinical trial testing.