Discovery of Potential Bladder Cancer Biomarkers by Comparative Urine Proteomics and Analysis

Lei, Ting; Zhao, Xuhong; Jin, Sheng; Meng, Qian; Zhou, Hui; Zhang, Man

doi:10.1016/j.clgc.2012.06.003

Cited by 71 publications

(54 citation statements)

References 34 publications

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“…Several of the biomarkers included in the classifiers were previously reported as biomarkers for the detection of urothelial bladder cancer. Apolipoprotein A-I peptide fragments were found up-regulated in both primary and recurrent disease in line with earlier reported findings on this protein in urothelial bladder cancer following application of two-dimensional electrophoresis (2-DE), or iTRAQ/LC-MS/MS-based proteomics analysis (28)(29)(30)(31)(32)(33)(34)(35). In addition, Fibrinogen chains a and b, well known urinary biomarkers for the detection of bladder cancer (30,31,(33)(34)(35), were also found at increased levels in urine from patients with urothelial bladder cancer and included in the classifiers.…”

Section: Discussionsupporting

confidence: 75%

“…In addition, Fibrinogen chains a and b, well known urinary biomarkers for the detection of bladder cancer (30,31,(33)(34)(35), were also found at increased levels in urine from patients with urothelial bladder cancer and included in the classifiers. Beta-2-macroglobulin and basement membrane-specific heparan sulfate proteoglycan core protein (HSPG2) were also confirmed with decreased excretion levels in urine from patients with urothelial bladder cancer, in line with previously reported proteomics data (28,31,33). Moreover, PGMRC1 (membrane-associated progesterone receptor component 1) has been previously included as a peptide biomarker in a CE-MS classifier discriminating between NMIBC and MIBC patients (14).…”

Section: Discussionsupporting

confidence: 57%

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Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study

Frantzi

Kessel

Zwarthoff

et al. 2016

Clinical Cancer Research

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Purpose: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted.Experimental Design: Two studies (total n ¼ 1,357) were performed for detecting primary (n ¼ 721) and relapsed urothelial bladder cancer (n ¼ 636). Cystoscopy was applied for detecting urothelial bladder cancer, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine-based peptide biomarker panels were derived from nested cross-sectional studies in primary (n ¼ 451) and recurrent (n ¼ 425) urothelial bladder cancer.Results: Two biomarker panels were developed on the basis of 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n ¼ 270) and recurrent urothelial bladder cancer (n ¼ 211), respectively. At the optimal threshold, the classifier for detecting primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC ¼ 0.87).Conclusions: The developed urine-based peptide biomarker panel for detecting primary urothelial bladder cancer exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 57%

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study

Frantzi

Kessel

Zwarthoff

et al. 2016

Clinical Cancer Research

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“…Furthermore, when ELISA assays were applied to assess the performance of apolipoprotein A-I as a diagnostic biomarker of bladder cancer in a total of 156 individuals with or without urological diseases, sensitivity of 91.6% and specificity of 85.7% was reported. 45 Reports from two other studies 42,43 confirmed these findings, demonstrating an increased level of apolipoprotein A-I in urine samples from patients with bladder cancer compared with those from healthy individuals. Besides apolipoprotein A-I, 11 additional proteins were found to be associated with bladder cancer using mass spectrometry.…”

Section: Electrophoresis-based Approachessupporting

confidence: 64%

“…Besides apolipoprotein A-I, 11 additional proteins were found to be associated with bladder cancer using mass spectrometry. 42 However, only apolipoprotein A-I was further evaluated and verified using western blot. 42 In a combined analysis of urinary and tissue proteomics data, cystatin-B was identified as a potential biomarker of bladder cancer.…”

Section: Electrophoresis-based Approachesmentioning

confidence: 99%

Developing proteomic biomarkers for bladder cancer: towards clinical application

et al. 2015

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Clinical use of proteomic biomarkers has the potential to substantially improve the outcomes of patients with bladder cancer. An unmet clinical need evidently exists for noninvasive biomarkers, which might enable improvements in both the diagnosis and prognosis of patients with bladder cancer, as well as improved monitoring of patients for the presence of recurrence. Urine is considered the optimal noninvasive source of proteomic biomarkers in patients with bladder cancer. Currently, a number of single-protein biomarkers have been detected in urine and tissue using a variety of proteomic techniques, each having specific conceptual considerations and technical implications. Promising preclinical data are available for several of these proteins; however, the combination of single urinary proteins into multimarker panels might better encompass the molecular heterogeneity of bladder cancer within this patient population, and prove more effective in clinical use.

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“…We previously identified apolipoprotein A-I as a potential biomarker, showing a strong statistical association of this blood-associated protein with bladder cancer (7,9). This linkage probably reflects that bleeding, secretion, and/or angiogenesis mechanisms are associated with bladder tumor.…”

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confidence: 99%

Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer

Chen

Chung

et al. 2015

Molecular & Cellular Proteomics

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More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ϳ150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins-SLC3A2, STMN1, and TAGLN2-in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC ‫؍‬ 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with agematched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n ‫؍‬ 205). Overall, TAGLN2 showed the most significant overexpression in individual bladder cancer tissues and urine specimens, and thus represents a potential biomarker for noninvasive screening for bladder cancer. Our findings highlight the value of bladder tissue proteome in providing valuable information for future validation studies of potential biomarkers in urothelial carcinoma. Molecular & Cellular Proteomics

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Discovery of Potential Bladder Cancer Biomarkers by Comparative Urine Proteomics and Analysis

Cited by 71 publications

References 34 publications

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study

Development and Validation of Urine-based Peptide Biomarker Panels for Detecting Bladder Cancer in a Multi-center Study

Developing proteomic biomarkers for bladder cancer: towards clinical application

Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer

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