TY - JOUR
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 R.
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 J.
AU - Jorgensen, Lars N.
AU - Klaeke, Michael
AU - Laurberg, Soren
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 - blood-based biomarkers
KW - colorectal cancer
KW - detection
UR - http://www.scopus.com/inward/record.url?scp=85010711367&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ijc.30558
DO - https://doi.org/10.1002/ijc.30558
M3 - 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 -