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Distinct urinary glycoprotein signatures in prostate cancer patients.

ABSTRACT: Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. Here, we describe a glycoproteomics strategy for deep quantitative mapping of N- and O-glycoproteins in urine with a view to investigate the diagnostic value of the glycoproteome to discriminate PCa from benign prostatic hyperplasia (BPH), two conditions that remain difficult to clinically stratify. Total protein extracts were obtained, concentrated and digested from urine of six PCa patients (Gleason score 7) and six BPH patients. The resulting peptide mixtures were TMT-labeled and mixed prior to a multi-faceted sample processing including hydrophilic interaction liquid chromatography (HILIC) and titanium dioxide SPE based enrichment, endo-/exoglycosidase treatment and HILIC-HPLC pre-fractionation. The isolated N- and O-glycopeptides were detected and quantified using high resolution mass spectrometry. We accurately quantified 729 N-glycoproteins spanning 1,310 unique N-glycosylation sites and observed 954 and 965 unique intact N- and O-glycopeptides, respectively, across the two disease conditions. Importantly, a panel of 56 intact N-glycopeptides perfectly discriminated PCa and BPH (ROC: AUC = 1). This study has generated a panel of intact glycopeptides that has a potential for PCa detection.

SUBMITTER: Kawahara R

PROVIDER: S-EPMC6145689 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Distinct urinary glycoprotein signatures in prostate cancer patients.

Kawahara Rebeca R Ortega Fabio F Rosa-Fernandes Livia L Guimarães Vanessa V Quina Daniel D Nahas Willian W Schwämmle Veit V Srougi Miguel M Leite Katia R M KRM Thaysen-Andersen Morten M Larsen Martin R MR Palmisano Giuseppe G

Oncotarget 20180904 69

Novel biomarkers are needed to complement prostate specific antigen (PSA) in prostate cancer (PCa) diagnostic screening programs. Glycoproteins represent a hitherto largely untapped resource with a great potential as specific and sensitive tumor biomarkers due to their abundance in bodily fluids and their dynamic and cancer-associated glycosylation. However, quantitative glycoproteomics strategies to detect potential glycoprotein cancer markers from complex biospecimen are only just emerging. He ...[more]

PMID: 30237853

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Project description:BackgroundCancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers.MethodsIn order to investigate CAF-related genes associated with radiotherapy and construct prognostic CAF-related gene signatures for prostate cancer, we firstly established a radio-resistant prostate CAF cell subline (referred to as CAFR) from Mus-CAF (referred to as CAF) through fractionated irradiation using X-rays. Transcriptome sequencing for CAF and CAFR was conducted, and 2626 CAF-related differentially expressed genes (DEGs) associated with radiotherapy were identified. Human homologous genes of mouse CAF-related DEGs were then obtained.ResultsFunctional enrichment analysis revealed that these CAF-related DEGs were significantly enriched ECM- and immune-related functions and pathways. Based on GSE116918 dataset, 186 CAF-related DEGs were correlated with biochemical recurrence-free survival (BCRFS) of prostate cancer patients, 16 of which were selected to construct a BCRFS-related CAF signature, such as ACPP, THBS2, and KCTD14; 142 CAF-related DEGs were correlated with metastasis-free survival (MFS), 16 of which were used to construct a MFS-related CAF signature, such as HOPX, TMEM132A, and ZNF467. Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients. The risk scores were higher in patients with higher gleason grades and higher clinical T stages. Moreover, the BCRFS-related CAF signature was an independent prognostic factor and a nomogram consisting of BCRFS-related CAF signature and various clinical factors accurately predicted 2-, 3-, and 5-year survival time of prostate cancer patients. Furthermore, the risk score was positively correlated with multiple immune checkpoints.ConclusionsOur established CAF signatures could accurately predict BCRFS and MFS in prostate cancer patients undergoing radiotherapy.

Dataset Information

Distinct urinary glycoprotein signatures in prostate cancer patients.

Publications

Distinct urinary glycoprotein signatures in prostate cancer patients.

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