Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers

Michael Wilhelmsen; Ib J. Christensen; Louise Rasmussen; Lars N. Jørgensen; Mogens Rørbæk Madsen; Jesper Vilandt; Thore Hillig; Michael Klærke; Knud T. Nielsen; Søren Laurberg; Nils Brünner; Susan Gawel; Xiaoqing Yang; Gerard Davis; Annemieke Heijboer; Frans Martens; Hans Jørgen Nielsen

doi:10.1002/ijc.30558

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers

Michael Wilhelmsen, Ib J. Christensen, Louise Rasmussen, Lars N. Jørgensen, Mogens Rørbæk Madsen, Jesper Vilandt, Thore Hillig, Michael Klærke, Knud T. Nielsen, Søren Laurberg, Nils Brünner, Susan Gawel, Xiaoqing Yang, Gerard Davis, Annemieke Heijboer, Frans Martens, Hans Jørgen Nielsen

18 Citations (Scopus)

Abstract

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.

Original language	English
Journal	International Journal of Cancer
Volume	140
Issue number	6
Pages (from-to)	1436-1446
Number of pages	11
ISSN	0020-7136
DOIs	https://doi.org/10.1002/ijc.30558
Publication status	Published - 15 Mar 2017

Keywords

Journal Article

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Wilhelmsen, M., Christensen, I. J., Rasmussen, L., Jørgensen, L. N., Madsen, M. R., Vilandt, J., Hillig, T., Klærke, M., Nielsen, K. T., Laurberg, S., Brünner, N., Gawel, S., Yang, X., Davis, G., Heijboer, A., Martens, F., & Nielsen, H. J. (2017). Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers. International Journal of Cancer, 140(6), 1436-1446. https://doi.org/10.1002/ijc.30558

Wilhelmsen, M, Christensen, IJ, Rasmussen, L, Jørgensen, LN, Madsen, MR, Vilandt, J, Hillig, T, Klærke, M, Nielsen, KT, Laurberg, S, Brünner, N, Gawel, S, Yang, X, Davis, G, Heijboer, A, Martens, F & Nielsen, HJ 2017, 'Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers', International Journal of Cancer, vol. 140, no. 6, pp. 1436-1446. https://doi.org/10.1002/ijc.30558

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abstract = "Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT{\textregistered} automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.",

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year = "2017",

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doi = "10.1002/ijc.30558",

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T1 - Detection of colorectal neoplasia

T2 - Combination of eight blood-based, cancer-associated protein biomarkers

AU - Wilhelmsen, Michael

AU - Christensen, Ib J.

AU - Rasmussen, Louise

AU - Jørgensen, Lars N.

AU - Madsen, Mogens Rørbæk

AU - Vilandt, Jesper

AU - Hillig, Thore

AU - Klærke, Michael

AU - Nielsen, Knud T.

AU - Laurberg, Søren

AU - Brünner, Nils

AU - Gawel, Susan

AU - Yang, Xiaoqing

AU - Davis, Gerard

AU - Heijboer, Annemieke

AU - Martens, Frans

AU - Nielsen, Hans Jørgen

PY - 2017/3/15

Y1 - 2017/3/15

N2 - Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.

AB - Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform. Primary endpoints were detection of (i) CRC and high-risk adenoma and (ii) CRC. Logistic regression was performed. Final reduced models were constructed selecting the four biomarkers with the highest likelihood scores. Subjects (N = 4,698) were consecutively included during 2010-2012. Colonoscopy detected 512 CRC patients, 319 colonic cancer and 193 rectal cancer. Extra colonic malignancies were detected in 177 patients, 689 had adenomas of which 399 were high-risk, 1,342 had nonneoplastic bowell disease and 1,978 subjects had 'clean' colorectum. Univariable analysis demonstrated that all biomarkers were statistically significant. Multivariate logistic regression demonstrated that the blood-based biomarkers in combination significantly predicted the endpoints. The reduced model resulted in the selection of CEA, hs-CRP, CyFra21-1 and Ferritin for the two endpoints; AUCs were 0.76 and 0.84, respectively. The postive predictive value at 90% sensitivity was 25% for endpoint 1 and the negative predictive value was 93%. For endpoint 2, the postive predictive value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC.

KW - Journal Article

U2 - 10.1002/ijc.30558

DO - 10.1002/ijc.30558

M3 - Journal article

C2 - 27935033

SN - 0020-7136

VL - 140

SP - 1436

EP - 1446

JO - International Journal of Cancer

JF - International Journal of Cancer

IS - 6

ER -

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers

Abstract

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