Clinical Proteomics of Biofluids in Haematological Malignancies

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.

Keywords: biofluids; biomarkers; haematological malignancies; leukaemia; lymphoma; multiple myeloma; proteomics.

Figure 1

Biofluids are easily accessible and suitable for proteomic analysis in a clinical setting. Red font indicates promising protein biomarkers in haematological malignancies identified in the corresponding biofluid. CXCL13, C-X-C motif chemokine ligand 13; IL-10, interleukin 10; S100A8/A9, S100 calcium-binding protein A8/A9; FABP5, fatty acid binding protein 5; 2-HG, 2-hydroxyglutarate; NGAL, neutrophil gelatinase-associated lipocalin; BDNF, brain-derived neurotrophic factor. Created using BioRender.

Figure 2

Schematic illustrating the steps involved in the detection of protein biomarkers in biofluids and their applications in a clinical setting. HAP, high-abundance protein; LAP, low-abundance protein; CTC, circulating tumour cell; ELISA, enzyme-linked immunosorbent assay; EpCAM, epithelial cell adhesion molecule; CK, cytokeratin. * Dynamic range of corresponding biofluid. Created using BioRender.