Plasma TIMP-1 and CEA as Markers for Detection of Primary Colorectal Cancer: A Prospective Validation Study Including Symptomatic and Non-symptomatic Individuals

Anticancer Res. 2015 Sep;35(9):4935-41.

Abstract

Background/aim: The combination of plasma tissue inhibitor of metalloproteinases-1 (1) and CEA has been shown to have utility in early detection of colorectal cancer (2). A prospective study was performed to validate previous findings.

Patients and methods: Individuals undergoing large bowel endoscopy were prospectively included (N=1965). Baseline data and co-morbidity were recorded. The primary end-point was the detection of CRC. Plasma was obtained before endoscopy and TIMP-1 and CEA levels were determined using an automated analysis platform when all samples were collected.

Results: CRC was detected in 32 individuals, 24 with colonic cancer (CC) and 8 with rectal cancer (RC). Other findings were 265 with adenomas and 889 with non-neoplastic pathology. The biomarker levels were elevated in plasma from patients with CRC, but also from patients with various co-morbidities compared to individuals without any findings at endoscopy. Univariate analysis demonstrated that both markers were significant predictors of CRC. The odds ratios (OR) for an elevated TIMP-1 level for the detection of CRC was 6.2 [95% confidence interval (CI)=3.1-13.0, p<0.0001] and for an elevated CEA level was 2.4 (95% CI=1.9-2.9, p<0.0001). A subset analysis with CC as the end-point showed an OR for TIMP-1 of 7.0 (95% CI=3.2-15.3, p<0.0001). Multivariable analysis including TIMP-1, CEA and age resulted in an OR for TIMP-1 of 2.0 (95% CI=0.7-5.2, p=0.078) and for CEA the OR was 2.2 (95% CI=1.8-2.8, p<0.0001).

Conclusion: This prospective study validates a previous study testing the detection of CRC based on TIMP-1 and CEA levels (3).

Keywords: Colorectal cancer; biomarkers; bowel endoscopy; early detection; screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Carcinoembryonic Antigen / blood*
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / enzymology*
  • Endoscopy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Reproducibility of Results
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1