scholarly journals Glycosylation: Rising Potential for Prostate Cancer Evaluation

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3726
Author(s):  
Anna Kałuża ◽  
Justyna Szczykutowicz ◽  
Mirosława Ferens-Sieczkowska
Keyword(s):  
Prostate Cancer ◽  
Cancer Detection ◽  
Protein Function ◽  
Cell Signalling ◽  
Specific Antigen ◽  
Protein Glycosylation ◽  
Biological Processes ◽  
Wide Range ◽  
Core Fucosylation ◽  
Modify Protein

Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and cellular metabolism. In this review, we summarize studies evaluating the prostate cancer associated glycosylation related alterations in sialylation, mainly α2,3-sialylation, core fucosylation, branched N-glycans, LacdiNAc group and presence of truncated O-glycans (sTn, sT antigen). Finally, we discuss the great potential to make use of glycans as diagnostic and prognostic biomarkers for prostate cancer.

scholarly journals Glycans as Biomarkers in Prostate Cancer

2019 ◽  
Vol 20 (6) ◽  
pp. 1389 ◽  
Author(s):  
Emma Scott ◽  
Jennifer Munkley
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Liquid Biopsies ◽  
Multifaceted Approach ◽  
Disease Biomarkers ◽  
High Profile ◽  
Psa Testing ◽  
Wide Range ◽  
Multifocal Disease ◽  
Core Fucosylation

Prostate cancer is the most commonly diagnosed malignancy in men, claiming over350,000 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-harmfuldisease. Hence, there is an urgent unmet clinical need to identify new diagnostic and prognosticbiomarkers. As prostate cancer is a heterogeneous and multifocal disease, it is likely that multiplebiomarkers will be needed to guide clinical decisions. Fluid-based biomarkers would be ideal, andattention is now turning to minimally invasive liquid biopsies, which enable the analysis oftumour components in patient blood or urine. Effective diagnostics using liquid biopsies willrequire a multifaceted approach, and a recent high-profile review discussed combining multipleanalytes, including changes to the tumour transcriptome, epigenome, proteome, and metabolome.However, the concentration on genomics-based paramaters for analysing liquid biopsies ispotentially missing a goldmine. Glycans have shown huge promise as disease biomarkers, anddata suggests that integrating biomarkers across multi-omic platforms (including changes to theglycome) can improve the stratification of patients with prostate cancer. A wide range ofalterations to glycans have been observed in prostate cancer, including changes to PSAglycosylation, increased sialylation and core fucosylation, increased O-GlcNacylation, theemergence of cryptic and branched N-glyans, and changes to galectins and proteoglycans. In thisreview, we discuss the huge potential to exploit glycans as diagnostic and prognostic biomarkersfor prostate cancer, and argue that the inclusion of glycans in a multi-analyte liquid biopsy test forprostate cancer will help maximise clinical utility.

scholarly journals The role of the androgen receptor as a driver and mitigator of cellular stress

2020 ◽  
Vol 65 (2) ◽  
pp. R19-R33
Author(s):  
Dimitrios Doultsinos ◽  
Ian Mills
Keyword(s):  
Prostate Cancer ◽  
Protein Synthesis ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Prostate Gland ◽  
Specific Antigen ◽  
Nuclear Hormone Receptor ◽  
Biological Processes ◽  
Normal Prostate ◽  
Mtor Activity

Prostate cancer is a high-incidence male cancer, which is dependent on the activity of a nuclear hormone receptor, the androgen receptor (AR). Since the AR is required for both normal prostate gland development and for prostate cancer progression, it is possible that prostate cancer evolves from perturbations in AR-dependent biological processes that sustain specialist glandular functions. The archetypal example of course is the use of prostate specific antigen (PSA), an organ-type specific component of the normal prostate secretome, as a biomarker of prostate cancer. Furthermore, localised prostate cancer is characterised by a low proliferative index and a heterogenous array of somatic mutations aligned to a multifocal disease pattern. We and others have identified a number of biological processes that are AR dependent and represent aberrations in significant glandular processes. Glands are characterised by high rates of metabolic activity including protein synthesis supported by co-dependent processes such as glycosylation, organelle biogenesis and vesicle trafficking. Impairments in anabolic metabolism and in protein folding/processing will inevitably impose proteotoxic and oxidative stress on glandular cells and, in particular, luminal epithelial cells for which secretion is their primary function. As cancer develops there is also significant metabolic dysregulation including impaired negative feedback effects on glycolytic and anabolic activity under conditions of hypoxia and heightened protein synthesis due to dysregulated PI 3-kinase/mTOR activity. In this review we will focus on the components of the AR regulome that support cancer development as well as glandular functions focussing on the unfolded protein response and on regulators of mTOR activity.

An Estimate of Prostate Cancer Prevalence in Italy

2002 ◽  
Vol 88 (5) ◽  
pp. 367-369 ◽  
Author(s):  
Carlo La Vecchia ◽  
Paolo Bruzzi ◽  
Adriano Decadi ◽  
Franco Gaboardi ◽  
Peter Boyle
Keyword(s):  
Prostate Cancer ◽  
Advanced Disease ◽  
Specific Antigen ◽  
Cancer Prevalence ◽  
Previous Diagnosis ◽  
Wide Range ◽  
Range Of Variation

Estimates of the total number of men with a previous diagnosis of prostate cancer in Italy range from 55,000 to 135,000. This wide range of variation is largely due to uncertainties on the number of protein-specific antigen-detected, asymptomatic cases. The number of clinically detected cases, including cases with advanced disease, is less subject to uncertainty, with reasonable estimates ranging from 45,000 to 60,000.

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