Stability of the Human Plasma Proteome to Pre-Analytical Variability as Assessed by an Aptamer-Based Approach.

Variable processing and storage of whole blood and/or plasma are potential confounders in biomarker development and clinical assays. The goal of the study was to investigate how pre-analytical variables impact the human plasma proteome. Whole blood obtained from 16 apparently healthy individuals was collected in six EDTA tubes and processed randomly under six pre-analytical variable conditions including blood storage at 0°C or RT for 6h (B6h0C or B6hRT) before processing to plasma, plasma storage at 4°C or RT for 24h (P24h4C or P24hRT), low centrifugal force at 1,300 xg, (Lowxg), and immediate processing to plasma under 2,500 xg (control) followed by plasma storage at -80°C. An aptamer-based proteomic assay was performed to identify significantly changed proteins (fold change ≥ 1.2, P < 0.05, and FDR < 0.05) relative to the control from a total of 1305 proteins assayed. Pre-analytical conditions Lowxg and B6h0C resulted in the most plasma proteome changes with 200 and 148 proteins significantly changed, respectively. Only 36 proteins were changed under B6hRT. Conditions P24h4C and P24hRT yielded changes of 28 and 75 proteins, respectively. The complement system was activated in vitro under the conditions B6hRT, P24h4C, and P24hRT. The results suggest particular pre-analytical variables should be controlled for clinical measurement of specific biomarkers.

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