Eric Schiffer

University of Leipzig, Leipzig, Saxony, Germany

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Publications (64)193.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Due to comprehensive PSA screening, the incidence for prostate cancer (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics and prognostic tools to differentiate between insignificant and aggressive, fast growing tumors. With the proteome-based method presented here, we were able to distinguish PCa from BPH, chronic prostatitis and healthy controls with 83 % sensitivity and 67 % specificity. Furthermore, the methods discerned advanced PCa from local, organ-confined PCa in a group of patients with gleason score 7 (80 % sensitivity, 82 % specificity). Our proteomic approach is based on the analysis of low molecular weight polypeptides, identified as the endpoint of the naturally occuring liquefaction cascade in seminal plasma. For the first time using seminal plasma as a source, we analysed a complex network of interacting proteases and specific inhibitors, reflecting tumor biology specificity. Our diagnostic and prognostic tool is robust and easy to handle, and therefore it is well suitable for the laboratory and medical practice.
    Der Urologe 09/2013; 52(9):1251-5. · 0.46 Impact Factor
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    ABSTRACT: Extensive prostate specific antigen screening for prostate cancer generates a high number of unnecessary biopsies and over-treatment due to insufficient differentiation between indolent and aggressive tumours. We hypothesized that seminal plasma is a robust source of novel prostate cancer (PCa) biomarkers with the potential to improve primary diagnosis of and to distinguish advanced from indolent disease. In an open-label case/control study 125 patients (70 PCa, 21 benign prostate hyperplasia, 25 chronic prostatitis, 9 healthy controls) were enrolled in 3 centres. Biomarker panels a) for PCa diagnosis (comparison of PCa patients versus benign controls) and b) for advanced disease (comparison of patients with post surgery Gleason score <7 versus Gleason score >7) were sought. Independent cohorts were used for proteomic biomarker discovery and testing the performance of the identified biomarker profiles. Seminal plasma was profiled using capillary electrophoresis mass spectrometry. Pre-analytical stability and analytical precision of the proteome analysis were determined. Support vector machine learning was used for classification. Stepwise application of two biomarker signatures with 21 and 5 biomarkers provided 83% sensitivity and 67% specificity for PCa detection in a test set of samples. A panel of 11 biomarkers for advanced disease discriminated between patients with Gleason score 7 and organ-confined (<pT3a) or advanced (≥pT3a) disease with 80% sensitivity and 82% specificity in a preliminary validation setting. Seminal profiles showed excellent pre-analytical stability. Eight biomarkers were identified as fragments of N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase, prostatic acid phosphatase, stabilin-2, GTPase IMAP family member 6, semenogelin-1 and -2. Restricted sample size was the major limitation of the study. Seminal plasma represents a robust source of potential peptide makers for primary PCa diagnosis. Our findings warrant further prospective validation to confirm the diagnostic potential of identified seminal biomarker candidates.
    PLoS ONE 01/2013; 8(6):e67514. · 3.53 Impact Factor
  • D M Carty, E Schiffer, C Delles
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    ABSTRACT: Proteomics, the study of the proteins making up the proteome, has emerged in recent years as an important tool in several different fields of medical research for early disease detection, for assessment of response to treatment and for unravelling underlying pathophysiological mechanisms. Although the majority of patients with hypertension are treated in a similar manner, the causes underlying the condition are diverse, and often poorly understood. Genetic studies have implicated several different candidate genes, but it may be that examination of the 'downstream' products of genes, the proteins, will help to improve understanding of the link between the environmental and genetic effects that contribute towards development of hypertension. Proteomic studies can be performed quickly and reliably on several different sample types including plasma and urine, requiring minimal pre-test preparation. In this review, we will compare the different analytical platforms and technical issues involved in proteomic analysis. We will discuss existing studies of proteomics in hypertension, as well as related conditions such as renal disease, pre-eclampsia and coronary artery disease. We will also explore potential future applications of proteomics-based research, which may ultimately lead to improved population screening, monitoring of therapy and early detection of target organ damage.Journal of Human Hypertension advance online publication, 9 August 2012; doi:10.1038/jhh.2012.30.
    Journal of human hypertension 08/2012; · 2.80 Impact Factor
  • Carty DM, Schiffer E, Delles C
    Journal of Human Hypertension 08/2012; · 2.82 Impact Factor
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    ABSTRACT: Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE(-/-) mice to discover proteins with pathophysiological roles in atherogenesis and to identify urinary polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE(-/-) mice either on high fat diet (HFD) or chow diet was collected over 12 weeks; urine of wild type mice on HFD was used to exclude diet-related proteome changes. Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples identified 16 polypeptides specific for ApoE(-/-) mice on HFD. In a blinded test set, these polypeptides allowed identification of atherosclerosis at a sensitivity of 90% and specificity of 100%, as well as monitoring of disease progression. Sequencing of the discovered polypeptides identified fragments of α(1)-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated protein, and collagen. Using immunohistochemistry, α(1)-antitrypsin, EGF, and collagen type I were shown to be highly expressed in atherosclerotic plaques of ApoE(-/-) mice on HFD. Urinary excretion levels of collagen and α(1)-antitrypsin fragments also significantly correlated with intraplaque collagen and α(1)-antitrypsin content, mirroring plaque protein expression in the urine proteome. To provide further confirmation that the newly identified proteins are relevant in humans, the presence of collagen type I, α(1)-antitrypsin, and EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis in mice exemplifies the potential of a novel multimarker approach for the noninvasive detection of atherosclerosis and monitoring of disease progression. Furthermore, this approach represents a novel discovery tool for the identification of proteins relevant in murine and human atherosclerosis and thus also defines potential novel therapeutic targets.
    Molecular &amp Cellular Proteomics 02/2012; 11(7):M111.013847. · 7.25 Impact Factor
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    Molecular &amp Cellular Proteomics 02/2012; · 7.25 Impact Factor
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    ABSTRACT: High-grade vesicoureteral reflux (VUR, grade IV or V) is a risk factor for renal scarring, impaired renal function, and arterial hypertension. Voiding cystourethrography is the gold standard for detecting the severity of VUR. High-grade VUR is present in the minority of children with urinary tract infection (UTI), thus exposing the majority to invasive diagnostics that have no surgical consequence. We therefore aimed at establishing a noninvasive test to identify children with high-grade VUR. In a case-control study, a specific urinary proteome pattern was established by capillary electrophoresis coupled to mass spectrometry in 18 patients with primary VUR grade IV or V, distinguishing these from 19 patients without VUR after UTI. This proteome pattern was independently validated in a blinded cohort of 17 patients with VUR grade IV or V and 19 patients without VUR. Sensitivity in detecting VUR grade IV or V in the blinded study was 88%, specificity was 79%. The test's accuracy was independent of age, gender, and grade of VUR in the contralateral kidney. The odds ratio of suffering from VUR grade IV or V when tested positive was 28 (95% confidence interval: 4.5 to 176.0). This noninvasive test is ready for prospective validation in large cohorts with the aim of identifying those children with UTI and hydronephrosis in need of further invasive diagnostics, such as voiding cystourethrography, thus sparing most children without pathologic urinary proteome patterns from additional diagnostics.
    PEDIATRICS 02/2012; 129(2):e356-63. · 4.47 Impact Factor
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    ABSTRACT: ObjectIVES: Capillary electrophoresis mass spectrometry urinary proteome analysis for prostate cancer has been shown to be highly accurate in the detection of prostate cancer. The aim of the present study was to report our experience with routine application of this test in clinical practice and its cost-effectiveness. The urinary proteome analysis for prostate cancer test was carried out in 211 patients in outpatient centers. In 184 of them, data about their follow up and the test results were available for analysis. Prostate cancer was detected in 49 cases. The test correctly recognized 42 out of 49 tumor patients, showing a sensitivity of 86% (95% confidence interval 73-94). Of 135 prostate cancer-negative patients, 79 had a negative urinary proteome analysis for prostate cancer test (specificity 59% [79/135 95% confidence interval 50-66]). Negative and positive predictive values were 92% (95% confidence interval 84-96) and 43% (95% confidence interval 33-53), respectively. A statistically significant (P<0.0005) improvement in terms of diagnostic accuracy was observed in comparison with serum prostate-specific antigen and percent-free prostate-specific antigen. Whereas the urinary proteome analysis for prostate cancer test results agreed in 65.7% with follow-up reference results, prostate-specific antigen achieved 33.3% and percent-free prostate-specific antigen achieved 42.7%. Cost-effectiveness analysis showed that the urinary proteome analysis for prostate cancer strategy outperformed the biopsy approach as well as prostate-specific antigen tests. The non-invasive urinary proteome analysis for prostate cancer test appears to be a helpful addition to prostate cancer diagnostics for patients with suspicious prostate-specific antigen and/or digital-rectal examination.
    International Journal of Urology 11/2011; 19(2):118-25. · 1.73 Impact Factor
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    ABSTRACT: Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy. In this study, a multi-marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE-MS) peptide spectra in urine samples from 16 cases with subclinical acute T-cell-mediated tubulointerstitial rejection and 23 nonrejection controls. Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82-0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE-MS-based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase-8 (MMP-8). Biopsy stainings revealed matrix metalloproteinase-8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection. The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.
    PROTEOMICS - CLINICAL APPLICATIONS 06/2011; 5(5-6):322-33. · 1.81 Impact Factor
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    ABSTRACT: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease-specific peptide patterns in patients with choledocholithiasis (n 5 16), PSC (n 5 18), and CC (n 5 16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis [n 5 14], PSC [n 5 18] and CC [n 5 25]). Peptides were characterized by sequencing. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98, P 5 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) in the independent cohort, resulting in an AUC value of 0.87 (95% CI: 0.73-0.95, P 5 0.0001) in ROC analysis. Eight out of 10 samples of patients with CC complicating PSC were identified. Conclusion: Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC.
    Hepatology International 03/2011; 3(3-5):875-884. · 2.64 Impact Factor
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    ABSTRACT: In Western societies the process of aging is closely related to the onset of chronic diseases, such as coronary artery disease, diabetic nephropathy or different types of malignancies. Novel biomarkers are urgently needed to assist in managing these diseases. Parallel to technical advancements possibilities for the analysis of the human proteome for biomarkers have recently made considerable progress. In a first part, this article attempts to describe the main proteomic platform technologies, their advantages and disadvantages and will critically review proteomic study design aspects necessary to obtain valuable data, such as choosing suitable clinical specimens, data processing and mining. Physiological age-related alterations in the human proteome have been described and were similar to indolent changes associated with chronic diseases, in particular of the kidneys. Therefore, in a second part this review will introduce several examples for the application of clinical proteomics to aging itself and age-related diseases. Several recent proteome studies with clinically sound designs are available. These performed careful validation in blinded cohorts. It is anticipated that a boost in disease-related proteomic data is expected in the very near future. However, lessons of the past teach the strict adherence to proper technological approaches, appropriate statistics, and large databases to fulfil these high expectations.
    Maturitas 03/2011; 68(3):233-44. · 2.84 Impact Factor
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    ABSTRACT: Early detection of malignant biliary tract diseases, especially cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis (PSC), is very difficult and often comes too late to give the patient a therapeutic benefit. We hypothesize that bile proteomic analysis distinguishes CC from nonmalignant lesions. We used capillary electrophoresis mass spectrometry (CE-MS) to identify disease-specific peptide patterns in patients with choledocholithiasis (n = 16), PSC (n = 18), and CC (n = 16) in a training set. A model for differentiation of choledocholithiasis from PSC and CC (PSC/CC model) and another model distinguishing CC from PSC (CC model) were subsequently validated in independent cohorts (choledocholithiasis [n = 14], PSC [n = 18] and CC [n = 25]). Peptides were characterized by sequencing. Application of the PSC/CC model in the independent test cohort resulted in correct exclusion of 12/14 bile samples from patients with choledocholithiasis and identification of 40/43 patients with PSC or CC (86% specificity, 93% sensitivity). The corresponding receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.93 (95% confidence interval [CI]: 0.82-0.98, P = 0.0001). The CC model succeeded in an accurate detection of 14/18 bile samples from patients with PSC and 21/25 samples with CC (78% specificity, 84% sensitivity) in the independent cohort, resulting in an AUC value of 0.87 (95% CI: 0.73-0.95, P = 0.0001) in ROC analysis. Eight out of 10 samples of patients with CC complicating PSC were identified. CONCLUSION: Bile proteomic analysis discriminates benign conditions from CC accurately. This method may become a diagnostic tool in future as it offers a new possibility to diagnose malignant bile duct disease and thus enables efficient therapy particularly in patients with PSC.
    Hepatology 03/2011; 53(3):875-84. · 12.00 Impact Factor
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    ABSTRACT: Urinary peptidome changes and discrimination for potential renal glomerular and tubular damage after 6 wk of fenofibrate treatment were evaluated in 26 healthy subjects. Peptide profiling was performed in urine samples before and after treatment using high-resolution capillary electrophoresis coupled with electrospray ionization mass spectrometry. A panel of 88 fenofibrate-sensitive peptides was detected with a frequency of ≥50% before and after treatment. This was reduced to 36 peptides by repeating the comparison ten times by randomly excluding samples at each time-point. Nineteen peptides were consistent and reliable biomarkers after an additional comparison with an age and sex-matched subject control group. Levels of peptides identified as fragments of Collagen α-1 (I), Collagen α-1 (XVII), Collagen α-2 (VIII) or sodium/potassium-transporting ATPase subunit gamma were reduced after fenofibrate treatment. Classification scores for renal tubular and glomerular damages determined by support vector machine based biomarker models increased after treatment but remained below pathological score cutoff values. Fenofibrate treatment led to minor modifications of the urinary proteomic profile in a way that does not create safety issues affecting glomerular and tubular functions. Urinary peptide profiling proved to be appropriate to monitor drug pharmacological effects in a clinical setting.
    PROTEOMICS - CLINICAL APPLICATIONS 02/2011; 5(3-4):159-66. · 1.81 Impact Factor
  • J H H Ehrich, E Schiffer, J Drube
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    ABSTRACT: Due to its accessibility and availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics in urology and nephrology. Here, we review the published findings of a reproducible, high-resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins - ranging from 0.8 to 17.0 kDA - using samples from renal patients analyzed by capillary electrophoresis coupled to mass spectrometry (CE-MS). CE-MS identified children with urodynamically relevant ureteric junction obstruction, vesicoureteric reflux of grades IV and V, glomerulopathies, tubulopathies, and chronic kidney disease. Our analysis revealed that the incorporation of urinary proteome analysis in the initial evaluation of children with urinary tract abnormalities will avoid side effects of radiological imaging techniques, reduce costs, and increase the quality-adjusted life years in this patient population. CE-MS can be recommended for clinical prospective studies on the analysis of naturally occurring urinary peptides in children with urinary tract diseases.
    Der Urologe 02/2011; 50(2):170-9. · 0.46 Impact Factor
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    ABSTRACT: Chronic kidney disease (CKD) patients belong to the group of patients with a high prevalence of cardiovascular disease (CVD). Arterial calcification and aortic stiffness are currently used as surrogates for vascular alterations. However, still little is known about prediction and the patho-physiologic mechanisms leading to CVD. We applied capillary electrophoresis coupled mass spectrometry profiling to blood specimens collected from 34 CKD stage 5D patients suffering from vascular alterations to allow insights into the molecular pathology of the disease. Statistical comparison of plasma profiles from mild and severe CVD cases according to either arterial calcification or aortic stiffness unveiled 13 novel biomarkers for vascular disease. Tandem mass spectrometry identified four of these as fragments of collagen alpha-1 type I and III and one as fragment of apolipoprotein CIII. Integrated in a distinct pattern the candidates were validated using the moderate CVD cases among the 34 CKD patients (N=11) and an additional independent blinded cohort of CKD stage 4-5 patients (N=21), who all had not been considered during biomarker discovery. The panel distinguished mild and severe CVD with sensitivity of 89% and specificity of 67% in this independent cohort. This diagnostic phase I/II study supports the notion that vascular alterations are reflected by distinct changes in plasma profiles of CKD patients.
    Journal of Hypertension 02/2011; 29(4):783-90. · 4.22 Impact Factor

Publication Stats

1k Citations
193.20 Total Impact Points

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Institutions

  • 2013
    • University of Leipzig
      Leipzig, Saxony, Germany
  • 2012
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 2009–2012
    • Hannover Medical School
      Hanover, Lower Saxony, Germany
    • University of Colorado
      • Barbara Davis Center for Childhood Diabetes
      Denver, CO, United States
    • Mahidol University
      Krung Thep, Bangkok, Thailand
  • 2006–2011
    • Mosaiques Diagnostics and Therapeutics AG
      Hanover, Lower Saxony, Germany
  • 2010
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 2008–2010
    • University of Wisconsin, Madison
      • Department of Chemistry
      Madison, MS, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Universitätsklinikum Freiburg
      • Department of Cardiology and Angiology II
      Freiburg, Lower Saxony, Germany