Abstract

Since the emergence of high-throughput proteomic techniques and advances in clinical technologies, there has been a steady rise in the number of cancer-associated diagnostic, prognostic, and predictive biomarkers being identified and translated into clinical use. The characterisation of biofluids has become a core objective for many proteomic researchers in order to detect disease-associated protein biomarkers in a minimally invasive manner. The proteomes of biofluids, including serum, saliva, cerebrospinal fluid, and urine, are highly dynamic with protein abundance fluctuating depending on the physiological and/or pathophysiological context. Improvements in mass-spectrometric technologies have facilitated the in-depth characterisation of biofluid proteomes which are now considered hosts of a wide array of clinically relevant biomarkers. Promising efforts are being made in the field of biomarker diagnostics for haematologic malignancies. Several serum and urine-based biomarkers such as free light chains, β-microglobulin, and lactate dehydrogenase are quantified as part of the clinical assessment of haematological malignancies. However, novel, minimally invasive proteomic markers are required to aid diagnosis and prognosis and to monitor therapeutic response and minimal residual disease. This review focuses on biofluids as a promising source of proteomic biomarkers in haematologic malignancies and a key component of future diagnostic, prognostic, and disease-monitoring applications.

Highlights

  • A recently described multifunctional platform mitigates the destructive nature of inductively coupled plasma mass spectrometry (ICP-MS) for circulating tumour cells (CTCs) enumeration by incorporating aptamer-bound magnetic beads which facilitate CTC enumeration and the release of CTCs detected for further analysis

  • The challenges involved in characterising this proteome are similar to those faced when characterising the serum/plasma proteome, the predominant challenge being the presence of high-abundance protein (HAP) such as albumin and amylase, which contribute to at least 60% of the human salivary proteome [113]

  • A recent study revealed that the levels of the pro-inflammatory heterodimer, S100A8/A9, in saliva could discriminate between healthy, Sjogrens syndrome (SS), and mucosa-associated lymphoid tissue lymphoma (MALT-L), illustrating its potential as a salivary biomarker for the monitoring of SS progression [131]

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The use of quantitative proteomic protocols, such as mass spectrometry-based techniques for discovery and targeted analyses, facilitates the quantitation of these proteins to identify candidate biomarkers with altered abundances for potential clinical applications [2] Detecting and quantifying these protein markers in patient samples can contribute to an earlier diagnosis, a more accurate prognosis, and/or identifying therapeutic regimens that are more likely to benefit individual patients. Biofluids, such as serum, plasma, saliva, cerebrospinal fluid (CSF), urine, and bone marrow-conditioned media, are often considered reflections of a tumours’ molecular make-up, possessing genomic, transcriptomic, and proteomic indicators of disease (Figure 1).

Invasive procedure
Detecting Biomarkers in Serum and Plasma
Saliva
Exploring the Saliva Proteome
Proteomic Analysis of Human Saliva
Saliva Biomarkers in Haematological Malignancies
Bone Marrow Conditioned Media
Cerebrospinal Fluid
Findings
Conclusions
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