Abstract
Prostate cancer is the most commonly diagnosed malignancy in men, claiming over 350,000 lives worldwide annually. Current diagnosis relies on prostate-specific antigen (PSA) testing, but this misses some aggressive tumours, and leads to the overtreatment of non-harmful disease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognostic biomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiple biomarkers will be needed to guide clinical decisions. Fluid-based biomarkers would be ideal, and attention is now turning to minimally invasive liquid biopsies, which enable the analysis of tumour components in patient blood or urine. Effective diagnostics using liquid biopsies will require a multifaceted approach, and a recent high-profile review discussed combining multiple analytes, including changes to the tumour transcriptome, epigenome, proteome, and metabolome. However, the concentration on genomics-based paramaters for analysing liquid biopsies is potentially missing a goldmine. Glycans have shown huge promise as disease biomarkers, and data suggests that integrating biomarkers across multi-omic platforms (including changes to the glycome) can improve the stratification of patients with prostate cancer. A wide range of alterations to glycans have been observed in prostate cancer, including changes to PSA glycosylation, increased sialylation and core fucosylation, increased O-GlcNacylation, the emergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans. In this review, we discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkers for prostate cancer, and argue that the inclusion of glycans in a multi-analyte liquid biopsy test for prostate cancer will help maximise clinical utility.
Highlights
Prostate cancer is the most common cancer in men, and is a major clinical burden [1]
Fluid-based biomarkers would be ideal, and attention is turning to minimally invasive liquid biopsies, which enable the analysis of tumour components in patient biological fluids such as blood and urine
Metabolic rewiring during disease progression is believed to promote the downregulation of hexosamine biosynthetic pathway (HBP) in castrate-resistant disease, and in particular, loss of the Glucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) enzyme may serve as a marker of progression to castrate resistance [72]
Summary
Prostate cancer is the most common cancer in men, and is a major clinical burden [1]. Urine is an amenable bodily fluid for prostate cancer biomarker discovery. Ue to theirGgcllyoycmcoaspnyslleaaxtriieotynm, satihjtoeersdbpuirfiefilsdceiunntlg,tiabenlsodcsktthusedoefyxliipnferge[st1sh2io]e,nmbuo, ftahsnpadevcetihfbiacetegntlhyhecuorgesyeillsyatnuioonndceelenrsaztryumldiineeskdwb(Fietithgwiunreeteh1ne).gcTelylhlcis[a9in]s.s and Glycans are major building blocks of life [12], but have been hugely understudied (Figure 1). A wide range of alterations to glycans have been observed in prostate cancer, including changes to PSA glycosylation, increased sialylation and fucosylation, increased O-GlcNacylation, the emergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans [22,23,24] (see Tables 1–3 for more details). We discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkers for prostate cancer, and argue that it will be essential to include glycans as part of a multi-analyte liquid biopsy test
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