Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy

John E. Blume; Michael Wilhelmsen; Ryan W. Benz; Nils Brünner; Ib Jarle Christensen; Lisa J. Croner; Roslyn Dillon; Thore Hillig; Jeffrey J. Jones; Lars Nannestad Jørgensen; Athit Kao; Michael Klaerke; Søren Laurberg; Mogens R. Madsen; Knud T. Nielsen; Jesper Vilandt; Bruce E. Wilcox; Jia You; Hans J. Nielsen

doi:10.1373/jalm.2016.020271

Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy

John E. Blume, Michael Wilhelmsen, Ryan W. Benz, Nils Brünner, Ib Jarle Christensen, Lisa J. Croner, Roslyn Dillon, Thore Hillig, Jeffrey J. Jones, Lars Nannestad Jørgensen, Athit Kao, Michael Klaerke, Søren Laurberg, Mogens R. Madsen, Knud T. Nielsen, Jesper Vilandt, Bruce E. Wilcox, Jia You, Hans J. Nielsen

Abstract

Background: Well-collected and well-documented sample repositories are necessary for disease biomarker development. The availability of significant numbers of samples with the associated patient information enables biomarker validation to proceed with maximum efficacy and minimum bias. The creation and utilization of such a resource is an important step in the development of blood-based biomarker tests for colorectal cancer. Methods: We have created a subject data and biological sample resource, Endoscopy II, which is based on 4698 individuals referred for diagnostic colonoscopy in Denmark between May 2010 and November 2012. Of the patients referred based on 1 or more clinical symptoms of colorectal neoplasia, 512 were confirmed by pathology to have colorectal cancer and 399 were confirmed to have advanced adenoma. Using subsets of these sample groups in case-control study designs (300 patients for colorectal cancer, 302 patients for advanced adenoma), 2 panels of plasma-based proteins for colorectal cancer and 1 panel for advanced adenoma were identified and validated based on ELISA data obtained for 28 proteins from the samples. Results: One of the validated colorectal cancer panels was comprised of 8 proteins (CATD, CEA, CO3, CO9, SEPR, AACT, MIF, and PSGL) and had a validation ROC curve area under the curve (AUC) of 0.82 (CI 0.75-0.88). There was no significant difference in the performance between early- and late-stage cancer. The advanced adenoma panel was comprised of 4 proteins (CATD, CLUS, GDF15, SAA1) and had a validation ROC curve AUC of 0.65 (CI 0.56-0.74). Conclusions: These results suggest that the development of blood-based aids to colorectal cancer detection and diagnosis is feasible.

Original language	English
Journal	The Journal of Applied Laboratory Medicine
Volume	1
Issue number	2
Pages (from-to)	181-193
Number of pages	13
DOIs	https://doi.org/10.1373/jalm.2016.020271
Publication status	Published - 1 Sept 2016

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Blume, J. E., Wilhelmsen, M., Benz, R. W., Brünner, N., Christensen, I. J., Croner, L. J., Dillon, R., Hillig, T., Jones, J. J., Jørgensen, L. N., Kao, A., Klaerke, M., Laurberg, S., Madsen, M. R., Nielsen, K. T., Vilandt, J., Wilcox, B. E., You, J., & Nielsen, H. J. (2016). Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy. The Journal of Applied Laboratory Medicine, 1(2), 181-193. https://doi.org/10.1373/jalm.2016.020271

Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy. / Blume, John E.; Wilhelmsen, Michael; Benz, Ryan W. et al.
In: The Journal of Applied Laboratory Medicine, Vol. 1, No. 2, 01.09.2016, p. 181-193.

Research output: Contribution to journal › Journal article › Research › peer-review

Blume, JE, Wilhelmsen, M, Benz, RW, Brünner, N, Christensen, IJ, Croner, LJ, Dillon, R, Hillig, T, Jones, JJ, Jørgensen, LN, Kao, A, Klaerke, M, Laurberg, S, Madsen, MR, Nielsen, KT, Vilandt, J, Wilcox, BE, You, J & Nielsen, HJ 2016, 'Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy', The Journal of Applied Laboratory Medicine, vol. 1, no. 2, pp. 181-193. https://doi.org/10.1373/jalm.2016.020271

Blume JE, Wilhelmsen M, Benz RW, Brünner N, Christensen IJ, Croner LJ et al. Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy. The Journal of Applied Laboratory Medicine. 2016 Sept 1;1(2):181-193. doi: 10.1373/jalm.2016.020271

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title = "Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy",

abstract = "Background: Well-collected and well-documented sample repositories are necessary for disease biomarker development. The availability of significant numbers of samples with the associated patient information enables biomarker validation to proceed with maximum efficacy and minimum bias. The creation and utilization of such a resource is an important step in the development of blood-based biomarker tests for colorectal cancer. Methods: We have created a subject data and biological sample resource, Endoscopy II, which is based on 4698 individuals referred for diagnostic colonoscopy in Denmark between May 2010 and November 2012. Of the patients referred based on 1 or more clinical symptoms of colorectal neoplasia, 512 were confirmed by pathology to have colorectal cancer and 399 were confirmed to have advanced adenoma. Using subsets of these sample groups in case-control study designs (300 patients for colorectal cancer, 302 patients for advanced adenoma), 2 panels of plasma-based proteins for colorectal cancer and 1 panel for advanced adenoma were identified and validated based on ELISA data obtained for 28 proteins from the samples. Results: One of the validated colorectal cancer panels was comprised of 8 proteins (CATD, CEA, CO3, CO9, SEPR, AACT, MIF, and PSGL) and had a validation ROC curve area under the curve (AUC) of 0.82 (CI 0.75-0.88). There was no significant difference in the performance between early- and late-stage cancer. The advanced adenoma panel was comprised of 4 proteins (CATD, CLUS, GDF15, SAA1) and had a validation ROC curve AUC of 0.65 (CI 0.56-0.74). Conclusions: These results suggest that the development of blood-based aids to colorectal cancer detection and diagnosis is feasible.",

author = "Blume, {John E.} and Michael Wilhelmsen and Benz, {Ryan W.} and Nils Br{\"u}nner and Christensen, {Ib Jarle} and Croner, {Lisa J.} and Roslyn Dillon and Thore Hillig and Jones, {Jeffrey J.} and J{\o}rgensen, {Lars Nannestad} and Athit Kao and Michael Klaerke and S{\o}ren Laurberg and Madsen, {Mogens R.} and Nielsen, {Knud T.} and Jesper Vilandt and Wilcox, {Bruce E.} and Jia You and Nielsen, {Hans J.}",

year = "2016",

month = sep,

day = "1",

doi = "10.1373/jalm.2016.020271",

language = "English",

volume = "1",

pages = "181--193",

journal = "The Journal of Applied Laboratory Medicine",

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TY - JOUR

T1 - Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy

AU - Blume, John E.

AU - Wilhelmsen, Michael

AU - Benz, Ryan W.

AU - Brünner, Nils

AU - Christensen, Ib Jarle

AU - Croner, Lisa J.

AU - Dillon, Roslyn

AU - Hillig, Thore

AU - Jones, Jeffrey J.

AU - Jørgensen, Lars Nannestad

AU - Kao, Athit

AU - Klaerke, Michael

AU - Laurberg, Søren

AU - Madsen, Mogens R.

AU - Nielsen, Knud T.

AU - Vilandt, Jesper

AU - Wilcox, Bruce E.

AU - You, Jia

AU - Nielsen, Hans J.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - Background: Well-collected and well-documented sample repositories are necessary for disease biomarker development. The availability of significant numbers of samples with the associated patient information enables biomarker validation to proceed with maximum efficacy and minimum bias. The creation and utilization of such a resource is an important step in the development of blood-based biomarker tests for colorectal cancer. Methods: We have created a subject data and biological sample resource, Endoscopy II, which is based on 4698 individuals referred for diagnostic colonoscopy in Denmark between May 2010 and November 2012. Of the patients referred based on 1 or more clinical symptoms of colorectal neoplasia, 512 were confirmed by pathology to have colorectal cancer and 399 were confirmed to have advanced adenoma. Using subsets of these sample groups in case-control study designs (300 patients for colorectal cancer, 302 patients for advanced adenoma), 2 panels of plasma-based proteins for colorectal cancer and 1 panel for advanced adenoma were identified and validated based on ELISA data obtained for 28 proteins from the samples. Results: One of the validated colorectal cancer panels was comprised of 8 proteins (CATD, CEA, CO3, CO9, SEPR, AACT, MIF, and PSGL) and had a validation ROC curve area under the curve (AUC) of 0.82 (CI 0.75-0.88). There was no significant difference in the performance between early- and late-stage cancer. The advanced adenoma panel was comprised of 4 proteins (CATD, CLUS, GDF15, SAA1) and had a validation ROC curve AUC of 0.65 (CI 0.56-0.74). Conclusions: These results suggest that the development of blood-based aids to colorectal cancer detection and diagnosis is feasible.

AB - Background: Well-collected and well-documented sample repositories are necessary for disease biomarker development. The availability of significant numbers of samples with the associated patient information enables biomarker validation to proceed with maximum efficacy and minimum bias. The creation and utilization of such a resource is an important step in the development of blood-based biomarker tests for colorectal cancer. Methods: We have created a subject data and biological sample resource, Endoscopy II, which is based on 4698 individuals referred for diagnostic colonoscopy in Denmark between May 2010 and November 2012. Of the patients referred based on 1 or more clinical symptoms of colorectal neoplasia, 512 were confirmed by pathology to have colorectal cancer and 399 were confirmed to have advanced adenoma. Using subsets of these sample groups in case-control study designs (300 patients for colorectal cancer, 302 patients for advanced adenoma), 2 panels of plasma-based proteins for colorectal cancer and 1 panel for advanced adenoma were identified and validated based on ELISA data obtained for 28 proteins from the samples. Results: One of the validated colorectal cancer panels was comprised of 8 proteins (CATD, CEA, CO3, CO9, SEPR, AACT, MIF, and PSGL) and had a validation ROC curve area under the curve (AUC) of 0.82 (CI 0.75-0.88). There was no significant difference in the performance between early- and late-stage cancer. The advanced adenoma panel was comprised of 4 proteins (CATD, CLUS, GDF15, SAA1) and had a validation ROC curve AUC of 0.65 (CI 0.56-0.74). Conclusions: These results suggest that the development of blood-based aids to colorectal cancer detection and diagnosis is feasible.

U2 - 10.1373/jalm.2016.020271

DO - 10.1373/jalm.2016.020271

M3 - Journal article

VL - 1

SP - 181

EP - 193

JO - The Journal of Applied Laboratory Medicine

JF - The Journal of Applied Laboratory Medicine

IS - 2

ER -

Discovery and validation of plasma-protein biomarker panels for the detection of colorectal cancer and advanced adenoma in a Danish collection of samples from patients referred for diagnostic colonoscopy

Abstract

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