# Validation and Advanced Development of Albumin Oxidizability as a Marker of Plasma/Serum Integrity

> **NIH NIH R33** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2020 · $343,561

## Abstract

Project Summary/Abstract
Every year, improprieties and inconsistencies in pre-analytical handling and storage of blood plasma/serum
(P/S) specimens generate unacceptably large numbers of costly false leads in biomedical research. Experts in
the field are calling for this problem to be immediately stopped or at least minimized. The issue is particularly
important in the scope of NIH-sponsored research: A recent study found that out of 455 NCI-sponsored
extramural grants that relied on biospecimens, 63% employed pre-existing biospecimens—107 of which
involved pre-existing P/S. Surprisingly, no criteria for establishing pre-existing sample integrity have been set
and no quality thresholds exist that must be met before NCI (taxpayer) funds are spent on studies involving
pre-existing P/S. Exposure to the thawed state (which includes temporary storage at -20 °C) represents one of
the most common pre-analytical variables (PAVs) encountered by P/S. Considering the entire life of a research
specimen, no other PAV is more difficult to control and track—and, as demonstrated in the Research Strategy,
even the best standard operating procedures (SOPs) in the most respected hands cannot guarantee that all
specimens are handled ideally (i.e., in accord with the SOP). Our preliminary data argue that objective,
molecular-level evidence based on measurements of molecular damage—above and beyond sole reliance on
SOPs—is crucial to unambiguously establishing sample integrity. To date, however, no gold standard marker
of P/S integrity yet exists. The goal of this project is to validate a simple, inexpensive, rapid test requiring 10 µL
of P/S that provides a representative assessment of the oxidative damage that P/S proteins have incurred due
to exposure to the thawed state. The test is based on the fact that the relative abundance of S-cysteinylated
(oxidized) albumin (S-Cys-Alb) increases substantially over time (but to a maximum value) when P/S is
handled/stored above its freezing point of -30 °C. Thus by measuring S-Cys-Alb before and after an intentional
incubation period that causes S-Cys-Alb to hit its maximum value, the difference between these values, ΔS-
Cys-Alb, is then readily interpreted as inversely proportional to the degree of ex vivo oxidation that occurred
prior to the first measurement of S-Cys-Alb. Thus, for example, a ΔS-Cys-Alb value of zero would indicate a
badly mistreated sample. Herein we will validate ΔS-Cys-Alb as a marker of P/S integrity via four Specific
Aims: Specific Aim 1: Experimentally validate the predicted range of ΔS-Cys-Alb that can be expected from
freshly collected cancer patient plasma and serum samples. Specific Aim 2: Systematically map out how ΔS-
Cys-Alb behaves under “realistic” mistreatment conditions and link known, unstable cancer markers to ΔS-Cys-
Alb. Specific Aim 3: Conduct a blind challenge to quantify the ability of ΔS-Cys-Alb to identify biospecimen
mistreatment within cancer patient plasma and serum samples. A...

## Key facts

- **NIH application ID:** 9948594
- **Project number:** 5R33CA217702-03
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** CHAD R BORGES
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $343,561
- **Award type:** 5
- **Project period:** 2018-08-08 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948594

## Citation

> US National Institutes of Health, RePORTER application 9948594, Validation and Advanced Development of Albumin Oxidizability as a Marker of Plasma/Serum Integrity (5R33CA217702-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9948594. Licensed CC0.

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