Circulating Transthyretin is a Systems Biomarker: Retrospective Clinical Evaluations in 48 Types of Human Diseases
SSRN Electronic Journal(2021)
Abstract
Background: Most human diseases are systems diseases, and systems biomarkers will be powerful tools in facilitating the diagnosis, prognosis, and treatment effect monitoring of systems diseases. Circulating transthyretin (TTR) or prealbumin, one of the commonly ordered blood tests, has been indicated as a biomarker for cancers and non-cancer diseases. To test if TTR were a systems biomarker and the mechanisms of its regulation, TTR concentrations in 48 different types of human diseases and healthy controls were systematically analyzed in the current study. Methods: Serum TTR concentration was determined by the standard "Immune turbidimetric method" in the clinical laboratory of our hospital. TTR data from 137,305 independent tests of patients with 48 clinically defined diseases and 3,387 tests from healthy individuals who came to the hospital for physical examination during the past five years were retrieved. All data were statistically analyzed with SPSS v26, RStudio V.1.3.1073, and python libraries 3.8. Results: The mean and median values of serum TTR concentrations were significantly decreased (p<0.001) in 47 out of 48 diseases. However, the dynamic TTR concentration ranges were far exceeded that in healthy controls, including patients suffering uremia, the only disease that had significantly increased (p<0.001) TTR mean and median values. ROC analyses showed that TTR was a decent biomarker (AUC > 0.6) for 40 out of 48 diseases, and the highest AUCs were observed in sepsis (AUC 0.97), cirrhosis (AUC 0.97), and pancreatitis (AUC 0.94). Remarkably, the eight diseases with AUC < 0.6 were mainly kidney- and blood-related diseases with unconventional ROC curves and broad TTR concentration ranges. Furthermore, similar TTR concentration distributing patterns were present in the same category of diseases, such as different types of cancers, liver-related diseases, blood-related cancers and diseases, vascular diseases, autoimmune diseases, and kidney diseases. Conclusions : Significantly decreased TTR mean and median values were common in 47 out of 48 human diseases. The liver, kidney, blood, and pancreas were the major organs involved in regulating TTR concentrations. Systems swings between catabolic and anabolic phases explained the different dynamic TTR concentration ranges in different diseases. Overall facts plus ROC analysis indicated that TTR was a systems biomarker instead of a prognosis or malnutrition indicator used clinically during the past.
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Key words
Transthyretin,Tumor Microenvironment
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