Deep Dive on the Proteome of Human Body Fluids: A Valuable Data Resource for Biomarker Discovery

Abstract

Background/Aim: Body fluids are considered to be a rich source of disease biomarkers. Proteins in many body fluids have potential clinical applications for disease diagnostic and prognostic purposes. The aim of this study was to establish an in-depth multi-body fluid proteome. Materials and Methods: Ten body fluids associated with 8 types of cancers collected from 23 patients involved in 19 common diseases underwent liquid chromatography tandem mass spectrometry (MS) analysis after gel-based protein separation (SDS-PAGE) or peptide-based fractionations. Bioinformatic analysis, including principal component analysis (PCA), consensus clustering, and hierarchical clustering analysis were also performed. The biological function was determined using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: We profiled the proteome of ten body fluids, including ascites, bile, cerebrospinal fluid (CSF), hydrothorax, knee joint fluid (KJF), plasma, saliva, serum, tears, and urine. A total of 3,396 nonredundant proteins were identified, of which 304 were shared among ten body fluids, with common functions in focal adhesion and complement/coagulation cascades. A total of 41.5% (1,409) of the proteins were detected in only one body fluid and were closely related to their adjacent tissues by function. The functional analysis of the remaining 1,683 proteins showed that similar functions might be shared among different body fluids, which further highlighted the close connection of body fluids in the human body. Conclusion: A deep proteome of multi-body fluids originated from patients diagnosed with 19 common diseases provides a valuable data resource, and might indicate the potential application of body fluids for biomarker discovery.Human body fluids are considered rich sources of potential disease biomarkers because they are in direct contact with a variety of living tissues, which include plasma/serum, saliva, urine, cerebrospinal fluid (CSF), tear fluid, ascites, bile, hydrothorax and knee joint fluid (KJF). It is widely accepted that human body fluids contain disease-associated proteins that are secreted, shed, and emanated from pathological tissues across the body (1). In disease, highly altered protein expression profiles in body fluids may generate undeniable signatures and unwrapped fingerprints, which may provide insight into disease mechanisms. Therefore, body fluids have potential applicability for the early detection of disease, for the monitoring of its progression, and for therapeutic drug efficacy, especially for their adjacent diseased tissue.Proteomics is a powerful method for biomedical research. With the significant advances in mass spectrometry (MS) and proteomics technologies (2, 3), protein biomarker discovery has become one of the central applications of proteomics. In terms of disease diagnosis and prognosis, compared to tissue biopsy, human body fluids (e.g. blood, urine, tears, or saliva) appear to be more easy and attractive because of several key advantages, including lo...

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