Glycomic and glycoproteomic approaches :|bpotential tools for the improvement of the gold standard biomarker for prostate cancer diagnosis

Domènech García, Heura
Biomarkers of cancer have become the central stage for many scientists since last years. Because of the rapid emerging technologies, scientists can now understand these biological markers and apply them for the early detection of cancer. Thus, providing potential noninvasive, sensitive and reliable assays that, in fact, could reduce cost in health care and increase quality of life. A broadly used serum marker is the prostate-specific antigen (PSA), which is referred as the gold standard tumor marker for the diagnosis of prostate cancer (PCa). The PSA test consists in the monitoring of PSA levels in sera and an increase of its levels may indicate that an individual can have PCa. However, serum PSA levels are also high in other diseases, such as benign prostatic hyperplasia (BPH). Moreover, PSA assay cannot distinguish between non-aggressive and aggressive tumors. Many scientists, however, have started to focus on studying some biochemical characteristics of PSA, especially the glycosylation pattern of PSA which has shown to be altered in cancer. The recent fields of Glycomics and Glycoproteomics, which encompass glycan or glycoprotein enrichment and proteomics technologies, are developing more sensitive and high-throughput techniques for an in-depth and quantitative identification of specific glycosylation abnormalities in a complex biological sample. This work focuses on a broad literature review about several glycoproteomic and glycomic methodologies applied for improving the specificity of PSA as well as on searching through databases and using some bioinformatic tools, which are a key element for the analysis and characterization of PSA. Moreover, three approaches - ELLA, CE-ESI-MS and MALDI-TOF-MS - have been explained in-detail and discussed. Particularly, a comparison has been stablished between several methods and strategies by mentioning the different advantages and limitations that these approaches present. This paper shows that through the application of the distinct approaches, a tremendous amount of data about the heterogenous glycan composition of PSA was revealed and significant alterations in the glycosylation pattern were reported, when comparing samples of PSA driven from healthy or BPH individuals with PCa patients. Hence, suggesting that the glycosylation pattern of PSA might be more reliable and sensitive for PCa diagnosis than PSA test. Nonetheless, more efforts are required to consider PSA glycosylation as the new golden standard ​
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