Purpose: Tumor cells, including colorectal cancer (CRC), are able to produce and release matrix metalloproteinase 9 (MMP-9) which is involved in tumor invasion and metastasis. Natural tissue inhibitors of matrix metalloproteinases (TIMPs) regulate activity of MMPs and stimulate tumor growth and malignant transformation. The aim of the present study was to compare the clinical significance of serum MMP-9 with TIMP-1 in the diagnosis of CRC patients and in the differentiation between colorectal adenoma (CA) and cancer.
Methods: Serum MMP-9 and TIMP-1 were measured in 75 CRC patients, 35 CA, and 70 healthy subjects using enzyme-linked immunosorbent assay. Concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were determined by microparticle enzyme immunoassay.
Results: Serum levels of all proteins tested were significantly higher in CRC patients than in healthy subjects. Additionally, serum TIMP-1 was significantly higher in patients with CRC than in CA patients. Concentrations of TIMP-1 correlated with tumor stage, nodal involvement, presence of distant metastases, patients' survival, and tumor resectability. Diagnostic sensitivity of TIMP-1 was higher (61%) than those of other biomarkers (MMP-9, 55%; CEA, 39%; CA 19-9, 11%), and increased in combined use with MMP-9 (75%) or CEA (73%). The areas under receiver operating characteristic curves of TIMP-1 were larger than those of MMP-9.
Conclusions: Our findings suggest better usefulness of serum TIMP-1 than MMP-9 in the diagnosis of CRC, especially in the assessment of Duke's classification of tumor stage, survival of cancer patients, resectability of tumor, and in the differentiation between CA and cancer.