The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Abstract

Purpose: Colorectal cancer (CRC) is one of the most common and death related cancers in the world. Therefore, the early diagnosis of CRCremains with a great importance to prevent its further progression and increase survival rates. Colonoscopy and pathological examinationswhich are invasive and painful procedures, are needed to make a definitive diagnosis of CRC. The carcinoembryonic antigen (CEA) is particularlyused for postoperative follow-up of CRC patients. The imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors ofmetalloproteinases (TIMPs) leads to degradation of extracellular matrix which is the most important step in invasion and metastasis. It was alsoobserved that cyclooxygenase-2 (COX-2) has crucial roles in the development and progression of colorectal cancer. The purpose of our studyis to detect fecal and plasma MMP-7, COX-2, TIMP-1, and CEA protein levels in patients with colorectal cancer, colorectal polyps, and healthyindividuals, and assess their association with each other and with clinicopathological variables. We also aimed to evaluate plasma and fecalMMP-7, COX-2, TIMP-1, and CEA protein levels as potential diagnostic markers in colorectal carcinoma.Methods: Plasma and fecal samples were taken from patients with fifteen colorectal cancers, twenty-six colorectal polyps, and thirty-threehealthy volunteers. Protein extraction was carried out from fecal samples. Plasma and fecal MMP-7, TIMP-1, and COX-2 protein levels weredetermined by ELISA whereas plasma and fecal CEA protein levels were detected with CEIA.Results: Plasma and fecal CEA levels were significantly higher in CRC than the control. In addition, plasma TIMP-1 and plasma CEA levels weresignificantly elevated in cancer according to polyp group. We also detected decreased plasma MMP-7 levels in polyps compared to controlgroup. Positive correlations were observed among plasma COX-2 and TIMP-1 levels (r=0.571), fecal COX-2 and CEA levels (r=0.764) in CRC.However, no association was found between biochemical parameters and clinicopathological variables. ROC analysis for discriminating CRCfrom healthy controls showed that area under curves (AUC) for fecal and plasma CEA levels were 0.763 and 0.692, respectively. Plasma CEA(AUC=0.735), plasma TIMP-1 (AUC=0.706), and their combination (AUC=0.760) exhibited significant diagnostic performances to differentiateCRC from polyp. In discrimination colorectal polyps from healthy tissues, MMP-7 showed the highest AUC value (0.667).Conclusion: Here we suggested that plasma and fecal CEA protein levels may be potential predictive noninvasive markers for diagnosis ofcolorectal adenocarcinoma. In addition, plasma CEA and TIMP-1 are also valuable biomarker candidates in differentiating colorectal cancerfrom colorectal polyps.