Abstract
Simple SummaryAberrant protein glycosylation is a well-known hallmark of cancer and is associated with differential expression of enzymes such as glycosyltransferases and glycosidases. The altered expression of the enzymes triggers cancer cells to produce glycoproteins with specific cancer-related aberrations in glycan structures. Increasing number of data indicate that glycosylation patterns of PSA and other prostate-originated proteins exert a potential to distinguish between benign prostate disease and cancer as well as among different stages of prostate cancer development and aggressiveness. This review summarizes the alterations in glycan sialylation, fucosylation, truncated O-glycans, and LacdiNAc groups outlining their potential applications in non-invasive diagnostic procedures of prostate diseases. Further research is desired to develop more general algorithms exploiting glycobiology data for the improvement of prostate diseases evaluation.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.
Highlights
Prostate cancer was the second most commonly occurring cancer and the fifth leading cause of cancer death among men in 2020 [1,2]
The low sensitivity of tests developed so far encourages the use of a combination of several markers in the assay, suggesting that such a combination could constitute a biomarker panel for prostate cancer detection, as proposed by Yoneyama et al To identify clinically significant prostate cancer (CSPC), they evaluated the amount of LacdiNAc-glycosylated prostate-specific antigen (LDN-PSA) and LDN-PSA
Researchers are constantly working on new approaches to the early diagnosis of prostate cancer, risk prediction and disease treatment, and emphasizing that glycans can be a source of new, non-invasive biomarkers
Summary
Prostate cancer was the second most commonly occurring cancer and the fifth leading cause of cancer death among men in 2020 [1,2]. PSA screening for prostate cancer has limited sensitivity and specificity, which can lead to overdiagnosis and overtreatment of indolent disease, resulting in unnecessary, invasive biopsy and treatments for non-aggressive cancers [5,6]. In the following years serum PSA screening in association with digital rectal exam (DRE) and Gleason scoring of prostate biopsy samples was approved by the FDA for the early detection of prostate cancer [7]. Imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) have evaluated as a potential tool for staging prostate cancer in men before radical treatment. The sensitivity of PSMA PET/CT technique for the detection of metastases is reduced, presumably due to limitations in the spatial resolution of detecting small tumor deposits in primary and recurrent prostate cancer [12]. Presented work does not provide evident solutions for the selection of glycoepitopes that could effectively act as prognostic biomarkers, the studies available so far do not allow for such far-reaching conclusions
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