Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer

Abstract

Blood is a readily accessible biofluid containing a plethora of important proteins, nucleic acids, and metabolites that can be used as clinical diagnostic tools in diseases, including cancer. Like the on-going efforts for cancer biomarker discovery using the liquid biopsy detection of circulating cell-free and cell-based tumor nucleic acids, the circulatory proteome has been underexplored for clinical cancer biomarker applications. A comprehensive proteome analysis of human serum/plasma with high-quality data and compelling interpretation can potentially provide opportunities for understanding disease mechanisms, although several challenges will have to be met. Serum/plasma proteome biomarkers are present in very low abundance, and there is high complexity involved due to the heterogeneity of cancers, for which there is a compelling need to develop sensitive and specific proteomic technologies and analytical platforms. To date, liquid chromatography mass spectrometry (LC-MS)-based quantitative proteomics has been a dominant analytical workflow to discover new potential cancer biomarkers in serum/plasma. This review will summarize the opportunities of serum proteomics for clinical applications; the challenges in the discovery of novel biomarkers in serum/plasma; and current proteomic strategies in cancer research for the application of serum/plasma proteomics for clinical prognostic, predictive, and diagnostic applications, as well as for monitoring minimal residual disease after treatments. We will highlight some of the recent advances in MS-based proteomics technologies with appropriate sample collection, processing uniformity, study design, and data analysis, focusing on how these integrated workflows can identify novel potential cancer biomarkers for clinical applications.

The CD8+T Cell Noncytotoxic Antiviral Responses

“…In any case, full identification of the CD8 + T cell antiviral factor (CAF) will be a benefit to any group of investigators (section V) ( Table 4 ). This protein is stable and fits the definition of a low-abundance protein, similar to cancer biomarkers ( 365 ). Thus, proteomics approaches with better resolution are needed to identify such rare proteins.…”

“…However, detection of a low-abundance protein such as CAF even with sensitive mass spectrometry has not yet revealed the identity nor structure of this naturally occurring antiretroviral protein. This challenge is similar to that of finding other low-abundance proteins such as cancer biomarkers ( 365 ).…”

Cancer diagnostics based on plasma protein biomarkers: hard times but great expectations

“…Analyses of such markers will pose stringent requirements for the detection techniques applied. For example, parallel analyses of multiple biomarker proteins emanating from the same tissue and thus reinforcing each other can strengthen diagnostic accuracy by reducing risks of spurious results [2, [48][49][50]. Analysis of leakage markers from tumor tissue may also require greatly improved assay sensitivity as outlined below.…”

Tandem Mass Tag (TMT) Proteomic Analysis of Saliva in Horses with Acute Abdominal Disease

“…Proteomics can identify high numbers of proteins simultaneously and is therefore useful in identifying new biomarkers as well as individual component proteins and peptides in complex biological samples [ 16 , 17 ]. The use of tandem mass tag (TMT) in proteomics allows the relative simultaneous quantification of differentially labelled peptides, since each peptide is marked and distinguished by differences on its reporter ion masses [ 18 , 19 ].…”