Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

The development of more specific biomarkers for prostate cancer and/or high-risk prostate cancer is necessary, because the prostate-specific antigen test lacks specificity for the detection of prostate cancer and can lead to unnecessary prostate biopsies. Urine is a promising source for the development of new biomarkers of prostate cancer. Biomarkers derived from prostate cancer cells are released into prostatic fluids and then into urine. Urine after manipulation of the prostate is enriched with prostate cancer biomarkers, which include prostate cancer cells, DNAs, RNAs, proteins and other small molecules. The urinary prostate cancer antigen 3 test is the first Food and Drug Administration-approved RNA-based urinary marker, and it helps in the detection of prostate cancer on repeat biopsy. The SelectMDx test is based on messenger RNA detection of DLX1 and HOXC6 in urine after prostate massage, and helps in the detection of high-risk prostate cancer on prostate biopsy. Exosomes are extracellular vesicles with a diameter of 30-200 nm that are secreted from various types of cells. Urinary prostate cancer-derived exosomes also contain RNAs and proteins specific for prostate cancer (e.g. PCA3 and TMPRSS2-ERG), and could be promising sources of novel biomarker discovery. The ExoDx Prostate test is a commercially available test based on the detection of three genes (PCA3, ERG and SPDEF) in urinary exosomes. Advancement of comprehensive analysis (microarray, mass spectrometry and next-generation sequencing) has resulted in the discovery of several urinary biomarkers. Non-invasive urinary markers can help in the decision to carry out prostate biopsy or in the design of a therapeutic strategy.

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“…Urinary fucosylated PSA was also associated with the Gleason score. The AUC for the prediction of cancers with a Gleason score ≥7 was 0.72 …”

Section: Proteins In Urinementioning

confidence: 99%

Urinary biomarkers of prostate cancer

2018

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“…There are two major strategies for Fuc glycoproteins analyses: (1) targeted Fuc proteins measurement by ELISA, western/lectin blot, or mass spectrometry (MS) 6,13,14,16,19,20 and (2) large-scale Fuc glycoproteomes profiling by MS analysis. 8,10,18,21–24 The second approach may be more comprehensive as it facilitates the understanding of underlying mechanisms associated with tumorigenesis and metastasis as well as the discovery of novel potential biomarkers for early clinical diagnosis.…”

mentioning

confidence: 99%

“…46–48 Recently, tremendous efforts have focused on the discovery of novel biomarkers to improve the detection of Pca, particularly the identification of aberrant expression of protein glycoforms. 16,17,49–53 We have previously reported the expression of α (1,6) fucosyltransferase (FUT8), an enzyme that catalyzes the transfer of fucose from GDP-fucose to N-linked type complex glycopeptides, was elevated in prostate cancer tissue samples as well as in the aggressive Pca cell line, PC3, compared less aggressive to LNCaP cells. 54 Furthermore, using a lectin AAL-based immunoassay to detect Fuc glycoforms of glycoproteins in serum samples of Pca patients, we showed that the ratio of Fuc prostate-specific antigen was significantly increased in AG Pca in comparison to NAG Pca.…”

mentioning

confidence: 99%

Site-Specific Fucosylation Analysis Identifying Glycoproteins Associated with Aggressive Prostate Cancer Cell Lines Using Tandem Affinity Enrichments of Intact Glycopeptides Followed by Mass Spectrometry

Zhou

Yang

et al. 2017

Anal. Chem.

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Fucosylation (Fuc) of glycoproteins plays an important role in regulating protein function and has been associated with the development of several cancer types including prostate cancer (Pca). Therefore, the research of Fuc glycoproteins has attracted increasing attention recently in the analytical field. Herein, a strategy based on lectin affinity enrichments of intact glycopeptides followed by mass spectrometry has been established to evaluate the specificities of various Fuc-binding lectins for glycosite-specific Fuc analysis of nonaggressive (NAG) and aggressive (AG) Pca cell lines. The enrichment specificities of Fuc glycopeptides using lectins (LCA, PSA, AAL, LTL, UEA I, and AOL) and MAX extraction cartridges alone, or in tandem, were evaluated. Our results showed that the use of lectin enrichment significantly increased the ratio of fucosylated glycopeptides to total glycopeptides compared to MAX enrichment. Furthermore, tandem use of lectin followed by MAX increased the number of identifications of Fuc glycopeptides compared to using lectin enrichment alone. LCA, PSA, and AOL showed stronger binding capacity than AAL, LTL, and UEA I. Also, LCA and PSA bound specifically to core Fuc, whereas AOL, AAL, and UEA I showed binding to both core Fuc and branch Fuc. The optimized enrichment method with tandem enrichment of LCA followed by MAX (LCA-MAX) was then applied to examine the Fuc glycoproteomes in two NAG and two AG Pca cell lines. In total, 973 intact Fuc glycopeptides were identified and quantified from 252 Fuc proteins by using the tandem-mass-tags (TMT) labeling and nanoliquid chromatography–mass spectrometry (nanoLC–MS/MS) analysis. Further data analysis revealed that 51 Fuc glycopeptides were overexpressed more than 2-fold in AG cell lines compared to NAG cells. The analysis of protein core fucosylation has great potential for aiding our understanding of invasive activity of AG Pca and may lead to the development of diagnostic approaches for AG Pca.

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“…Urine is likely to become an increasingly powerful source of prostate-specific biomarkers [9][10][11][12]. Urine after DRE contains various markers originating from the prostate, including cytokines10, RNAs [13], DNAs [14], and prostate cells [11].…”

Section: Discussionmentioning

confidence: 99%

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

Fujita¹,

Kellogg²,

Charles³

et al. 2017

MCMR

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Abstract. Monocyte chemotactic protein-1 (MCP-1) is differentially expressed in benign prostatic hyperplasia (BPH) and is a potential clinical biomarker for BPH. We collected urine post-digital rectal examination (DRE) from 48 men who did not have a diagnosis of prostate cancer. We measured MCP-1 levels by enzyme-linked immunosorbent assay (ELISA) and compared them with prostate weight and lower urinary tract symptoms (LUTS) as measured by the International Prostate Symptom Score (I-PSS) utilizing correlation and regression analyses. In post-DRE urine, higher MCP-1 levels were associated with increased I-PSS but not with prostate volume. MCP-1 levels in men with prostate enlargement were significantly higher than those in men without enlargement. In multivariable regression adjusting for age, prostate volume, and PSA,higher urinary MCP-1 was associated with significantly higher I-PSS. Since MCP-1 is preferentially expressed in BPH tissue, these data suggest that MCP-1 may be a novel biomarker for clinically significant BPH.Keywords: MCP-1, LUTS, urine marker, benign prostatic hyperplasia IntroductionBenign prostate hyperplasia (BPH) is a common disease affecting older men caused by unregulated prostatic stromal and epithelial growth resulting in prostate enlargement, bladder outlet obstruction, and lower urinary tract symptoms (LUTS) [1]. Despite intensive researches over the last several decades, the molecular mechanisms underlying prostatic enlargement and symptomatic bladder outlet obstruction remain obscure, and specific clinical markers for symptomatic BPH have yet to be developed. We previously used a human cytokine array to search for cytokines in expressed prostatic secretions (EPS) from radical prostatectomy specimens that may be associated with prostate enlargement, and found that monocyte/macrophage chemoattractant protein-1 (MCP-1, CCL2) in EPS was associated with prostate size [2]. MCP-1 is a member of the CC chemokine superfamily and plays a critical role in the recruitment and activation of monocytes during inflammation [3]. MCP-1 is secreted from prostatic stromal cells and stimulates the proliferation of prostatic epithelial cells in vitro. Immunohistochemical studies indicated that MCP-1 was upregulated in benign prostatic hyperplasia (BPH) lesions, and MCP-1 levels in EPS correlated with mRNA levels of the macrophage marker CD68 [4]. Based on these data, we hypothesize that MCP-1 levels in urine after DRE, which is enriched in prostatic contents, could serve as a specific clinical marker for symptomatic BPH. Therefore, we evaluated associations of MCP-1 levels in urine collected after DRE with prostate volume and LUTS by enzyme-linked immunosorbent assay (ELISA).

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Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

Cited by 25 publications

References 14 publications

Urinary biomarkers of prostate cancer

Urinary biomarkers of prostate cancer

Site-Specific Fucosylation Analysis Identifying Glycoproteins Associated with Aggressive Prostate Cancer Cell Lines Using Tandem Affinity Enrichments of Intact Glycopeptides Followed by Mass Spectrometry

Prostatic Monocyte Chemotactic Protein-1 (MCP-1): A Novel Potential Biomarker for Symptomatic Benign Prostatic Hyperplasia

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