Plasma TIMP-1 and CEA in detection of primary colorectal cancer: a prospective, population based study of 4509 high-risk individuals.
OBJECTIVE
The combination of plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) and carcinoembryonic antigen (CEA) may be valuable biomarkers for early detection of colorectal cancer (CRC). A prospective, population based study was performed to validate this hypothesis.


METHODS
Individuals (n = 4509) referred for large bowel endoscopy due to symptoms of CRC were prospectively included. Baseline data and concurrent diseases were recorded. The primary endpoint was detection of CRC and findings at examinations were recorded using International Classification of Diseases-10 codes. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined after the inclusion of all individuals.


RESULTS
Findings were based on sigmoidoscopy in 1766 and colonoscopy in 2743 individuals. Colon cancer (CC) was detected in 184 and rectal cancer in 110 individuals. Ten individuals with other cancers, 856 with adenomas and 1176 with non-neoplastic findings were also detected. The biomarker levels were increased in a variety of diseases including CRC compared to individuals without any findings at endoscopy. A multivariable analysis demonstrated that both markers were significant and independent detectors of CRC. Combining both biomarkers, independent contributions from each (TIMP-1, odds ratio (OR) = 1.8 (95% confidence interval (CI): 1.4-2.2), p < 0.0001; CEA < 5 ng/ml, OR = 1.6, 1.3-1.9, or ≥ 5 ng/ml, OR = 2.3, 95% CI: 1.9-2.7 (p < 0.0001)) were obtained. Subgroup analysis of individuals examined by colonoscopy with CC as the endpoint showed that combining both biomarkers, independent contributions from each (TIMP-1, OR = 2.5, 95% CI: 1.8-3.4, p < 0.0001; CEA < 5 ng/ml, OR = 1.4, 95% CI: 1.1-1.8, and CEA ≥ 5 ng/ml, OR = 2.3, 95% CI: 1.8-3.0 (p < 0.0001)) were obtained.


CONCLUSIONS
This prospective validation study supports the use of the combination of plasma TIMP-1 and CEA protein measurements as a potential aid in early detection of CRC and specifically of CC.
Nielsen
Hans J
HJ
Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark. h.j.nielsen@ofir.dk
Brünner
Nils
N
Jorgensen
Lars N
LN
Olsen
Jesper
J
Rahr
Hans B
HB
Thygesen
Knud
K
Hoyer
Ute
U
Laurberg
Søren
S
Stieber
Petra
P
Blankenstein
Marinus A
MA
Davis
Gerard
G
Dowell
Barry L
BL
Christensen
Ib J
IJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D055815:Young Adult
D015415:Biomarkers; D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1