Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling

Michael Ehmann, Klaus Felix, Daniel Hartmann, Martina Schnolzer, Matthias Nees, Sonja Vorderwulbecke, Ralf Bogumi, Markus W. Buchler, Helmut Friess (Corresponding Author)

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Abstract

Objective: Early detection is the only promising approach to significantly improve the survival of patients with pancreatic cancer (PCa). Noninvasive tools for the diagnosis, prognosis, and monitoring of this disease are of urgent need. The purpose of this study was to identify and validate new biomarkers in PCa patient serum samples. Methods: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry has been applied to analyze serum protein alterations associated with PCa and to identify sets of potential biomarkers indicative for this disease. A cohort of 96 serum samples from patients undergoing PCa surgery was compared with sera from 96 healthy volunteers as controls. The sera were fractionated by anion exchange chromatography, and 3 of 6 fractions were analyzed onto 2 different chromatographic arrays. Results: Data analysis revealed 24 differentially expressed protein peaks (P < 0.001), of which 21 were downregulated in the PCa samples. The best single marker can predict 92% of the controls and 89% of the cancer samples correctly. In addition, multivariate pattern analysis was performed. The best pattern model using a set of 3 markers was obtained using fraction 6 on immobilized metal affinity capture, loaded with Cu-Cu arrays. With this pattern model, a sensitivity of 100% and a specificity of 98% for the training data set and a sensitivity of 83% and specificity of 77% for the test data set were achieved with the PCa group set as true positive. Several of protein peaks, including the best single marker at 17.27 kd and other proteins from the pattern models, were purified and identified by peptide mapping and postsource decay-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Apolipoprotein A-II, transthyretin, and apolipoprotein A-I were identified as markers, and these identified proteins were decreased at least 2-fold in PCa serum when compared with the control group. Conclusions: PCa is associated with a specific decrease of distinct serum proteins, which allows a reliable differentiation between pancreatic cancer and healthy controls.
Original languageEnglish
Pages (from-to)205-214
JournalPancreas
Volume34
Issue number2
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

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Pancreatic Neoplasms
Blood Proteins
Serum
Mass Spectrometry
Proteins
Lasers
Biomarkers
Apolipoprotein A-II
Prealbumin
Peptide Mapping
Apolipoprotein A-I
Anions
Chromatography
Healthy Volunteers
Down-Regulation
Multivariate Analysis
Metals
Sensitivity and Specificity
Control Groups
Survival

Cite this

Ehmann, M., Felix, K., Hartmann, D., Schnolzer, M., Nees, M., Vorderwulbecke, S., ... Friess, H. (2007). Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. Pancreas, 34(2), 205-214. https://doi.org/10.1097/01.mpa.0000250128.57026.b2
Ehmann, Michael ; Felix, Klaus ; Hartmann, Daniel ; Schnolzer, Martina ; Nees, Matthias ; Vorderwulbecke, Sonja ; Bogumi, Ralf ; Buchler, Markus W. ; Friess, Helmut. / Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. In: Pancreas. 2007 ; Vol. 34, No. 2. pp. 205-214.
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abstract = "Objective: Early detection is the only promising approach to significantly improve the survival of patients with pancreatic cancer (PCa). Noninvasive tools for the diagnosis, prognosis, and monitoring of this disease are of urgent need. The purpose of this study was to identify and validate new biomarkers in PCa patient serum samples. Methods: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry has been applied to analyze serum protein alterations associated with PCa and to identify sets of potential biomarkers indicative for this disease. A cohort of 96 serum samples from patients undergoing PCa surgery was compared with sera from 96 healthy volunteers as controls. The sera were fractionated by anion exchange chromatography, and 3 of 6 fractions were analyzed onto 2 different chromatographic arrays. Results: Data analysis revealed 24 differentially expressed protein peaks (P < 0.001), of which 21 were downregulated in the PCa samples. The best single marker can predict 92{\%} of the controls and 89{\%} of the cancer samples correctly. In addition, multivariate pattern analysis was performed. The best pattern model using a set of 3 markers was obtained using fraction 6 on immobilized metal affinity capture, loaded with Cu-Cu arrays. With this pattern model, a sensitivity of 100{\%} and a specificity of 98{\%} for the training data set and a sensitivity of 83{\%} and specificity of 77{\%} for the test data set were achieved with the PCa group set as true positive. Several of protein peaks, including the best single marker at 17.27 kd and other proteins from the pattern models, were purified and identified by peptide mapping and postsource decay-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Apolipoprotein A-II, transthyretin, and apolipoprotein A-I were identified as markers, and these identified proteins were decreased at least 2-fold in PCa serum when compared with the control group. Conclusions: PCa is associated with a specific decrease of distinct serum proteins, which allows a reliable differentiation between pancreatic cancer and healthy controls.",
author = "Michael Ehmann and Klaus Felix and Daniel Hartmann and Martina Schnolzer and Matthias Nees and Sonja Vorderwulbecke and Ralf Bogumi and Buchler, {Markus W.} and Helmut Friess",
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Ehmann, M, Felix, K, Hartmann, D, Schnolzer, M, Nees, M, Vorderwulbecke, S, Bogumi, R, Buchler, MW & Friess, H 2007, 'Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling', Pancreas, vol. 34, no. 2, pp. 205-214. https://doi.org/10.1097/01.mpa.0000250128.57026.b2

Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling. / Ehmann, Michael; Felix, Klaus; Hartmann, Daniel; Schnolzer, Martina; Nees, Matthias; Vorderwulbecke, Sonja; Bogumi, Ralf; Buchler, Markus W.; Friess, Helmut (Corresponding Author).

In: Pancreas, Vol. 34, No. 2, 2007, p. 205-214.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Identification of potential markers for the detection of pancreatic cancer through comparative serum protein expression profiling

AU - Ehmann, Michael

AU - Felix, Klaus

AU - Hartmann, Daniel

AU - Schnolzer, Martina

AU - Nees, Matthias

AU - Vorderwulbecke, Sonja

AU - Bogumi, Ralf

AU - Buchler, Markus W.

AU - Friess, Helmut

PY - 2007

Y1 - 2007

N2 - Objective: Early detection is the only promising approach to significantly improve the survival of patients with pancreatic cancer (PCa). Noninvasive tools for the diagnosis, prognosis, and monitoring of this disease are of urgent need. The purpose of this study was to identify and validate new biomarkers in PCa patient serum samples. Methods: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry has been applied to analyze serum protein alterations associated with PCa and to identify sets of potential biomarkers indicative for this disease. A cohort of 96 serum samples from patients undergoing PCa surgery was compared with sera from 96 healthy volunteers as controls. The sera were fractionated by anion exchange chromatography, and 3 of 6 fractions were analyzed onto 2 different chromatographic arrays. Results: Data analysis revealed 24 differentially expressed protein peaks (P < 0.001), of which 21 were downregulated in the PCa samples. The best single marker can predict 92% of the controls and 89% of the cancer samples correctly. In addition, multivariate pattern analysis was performed. The best pattern model using a set of 3 markers was obtained using fraction 6 on immobilized metal affinity capture, loaded with Cu-Cu arrays. With this pattern model, a sensitivity of 100% and a specificity of 98% for the training data set and a sensitivity of 83% and specificity of 77% for the test data set were achieved with the PCa group set as true positive. Several of protein peaks, including the best single marker at 17.27 kd and other proteins from the pattern models, were purified and identified by peptide mapping and postsource decay-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Apolipoprotein A-II, transthyretin, and apolipoprotein A-I were identified as markers, and these identified proteins were decreased at least 2-fold in PCa serum when compared with the control group. Conclusions: PCa is associated with a specific decrease of distinct serum proteins, which allows a reliable differentiation between pancreatic cancer and healthy controls.

AB - Objective: Early detection is the only promising approach to significantly improve the survival of patients with pancreatic cancer (PCa). Noninvasive tools for the diagnosis, prognosis, and monitoring of this disease are of urgent need. The purpose of this study was to identify and validate new biomarkers in PCa patient serum samples. Methods: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry has been applied to analyze serum protein alterations associated with PCa and to identify sets of potential biomarkers indicative for this disease. A cohort of 96 serum samples from patients undergoing PCa surgery was compared with sera from 96 healthy volunteers as controls. The sera were fractionated by anion exchange chromatography, and 3 of 6 fractions were analyzed onto 2 different chromatographic arrays. Results: Data analysis revealed 24 differentially expressed protein peaks (P < 0.001), of which 21 were downregulated in the PCa samples. The best single marker can predict 92% of the controls and 89% of the cancer samples correctly. In addition, multivariate pattern analysis was performed. The best pattern model using a set of 3 markers was obtained using fraction 6 on immobilized metal affinity capture, loaded with Cu-Cu arrays. With this pattern model, a sensitivity of 100% and a specificity of 98% for the training data set and a sensitivity of 83% and specificity of 77% for the test data set were achieved with the PCa group set as true positive. Several of protein peaks, including the best single marker at 17.27 kd and other proteins from the pattern models, were purified and identified by peptide mapping and postsource decay-matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Apolipoprotein A-II, transthyretin, and apolipoprotein A-I were identified as markers, and these identified proteins were decreased at least 2-fold in PCa serum when compared with the control group. Conclusions: PCa is associated with a specific decrease of distinct serum proteins, which allows a reliable differentiation between pancreatic cancer and healthy controls.

U2 - 10.1097/01.mpa.0000250128.57026.b2

DO - 10.1097/01.mpa.0000250128.57026.b2

M3 - Article

VL - 34

SP - 205

EP - 214

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 2

ER -