Evaluation of fecal and plasma timp-1,cox-2,mmp-7 combinations as a tumor marker in colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence increases progressively after the age of 50. Its early diagnosis is difficult because of its usually remain asymptomatic. The degradation of extracellular matrix is the most important step in invasion and metastasis. The imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMP) is important in the formation of invasion. Matrilizin (MMP-7) plays an inducing role in the transformation of colorectal polyps to cancer. It has been shown that MMP-7 increases in early-stage of colorectal cancer. TIMP-1 has also antiapoptotic effect which inhibits tumor growth. There are studies showing that TIMP-1 increases in colorectal cancer and has a higher sensitivity according to CEA. The sensitivities of fecal TIMP-1 and CEA in CRC was determined. It was shown that the increase of cyclooxygenase-2 (COX-2) is effective in the steps of colorectal carcinogenesis. The increase of COX-2 in colorectal cancer are shown in many studies. COX-2 and MMP-7 mRNA expression in the feces are shown in recent studies. CEA is the unique biochemical marker currently used in CRC. Due to the low specificity and sensitivity , it is used in follow-up but not in diagnosis. Fekal occult blood test is a noninvasive test to detect low sensitivity for CRC. Colonoscopy is used for diagnosis and it is uncomfortable, expensive and invasive procedure for patients.The purpose of this study is to quantify fecal and plasma MMP-7, COX-2, TIMP-1 and CEA levels in colorectal cancer, polyps and control patients and also to analyze the differences between these groups and the diagnostic value of these markers. In addition, we aimed to asses the relationship between clinicopathologic variables for cancer and polyps and MMP-7, COX-2, TIMP-1, CEA levels .For working group, plasma samples were taken from 33 controls, 23 polyps, 15 cancer patients and fecal samples were taken from 16 controls, 8 polyps, 8 cancer. Fecal supernatants obtained from extraction and plasma samples were determined by ELISA.Plasma TIMP-1, MMP-7, COX-2 levels were not observed statistically significant difference between control, polyps and cancer patients. Plasma CEA levels were significantly higher in the cancer group than control group (p = 0.008) and than polyp group (p = 0.012). There was no difference between plasma TIMP-1, MMP-7, COX-2, CEA levels and clinicopathological variables. There was no statistical correlation between fecal and plasma TIMP-1, MMP-7, COX-2, CEA levels. In the control and cancer group, the differences the area under the curve in ROC curve for plasma CEA, COX-2, TIMP-1 and MMP-7 are 0.728, 0.571, 0.480 and 0.359, respectively. Between polyps and cancer groups, the differences the area under the curve in ROC curve for plasma CEA, TIMP-1, MMP-7 and COX-2 are 0.735, 0.614, 0.516 and 0.396, respectively. Fecal CEA levels were higher in the cancer group than the control group (p = 0.027). Fecal TIMP-1, MMP-7, COX-2 levels were not observed statistically significant difference between control, polyps and cancer patients. For fecal CEA, MMP-7,TIMP-1 and COX-2 in cancer and the control group, the differences between the ROC curve area under the curve are 0.769, 0.466, 0.463 and 0.425. Between polyps and cancer group, the differences the area under the curve in ROC curve for fecal CEA, COX-2, MMP-7 and TIMP-1 are 0.750, 0.625, 0.438 and 0.196, respectively.As a result, plasma CEA levels are the unique marker in colorectal cancer. Plasma CEA, TIMP-1 and MMP-7 have value of diagnostic differentiation of colorectal cancer and polyps. Fecal CEA may be a new marker for colorectal cancer. Fecal TIMP-1 and COX-2 have diagnostic value of the distinguish from cancer to polyps. In order to increase the diagnostic value of plasma and fecal markers, a large-scale clinical studies are needed.Key words: colorectal cancer, fecal and plasma TIMP-1, MMP-7, COX-2, CEA, ELISA