Rabia KIYAK, Didem KELEŞ, Göksel BENGİ, Mustafa YALÇIN, Ömer TOPALAK, Gülgün OKTAY

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

Purpose: Colorectal cancer CRC is one of the most common and death related cancers in the world. Therefore, the early diagnosis of CRC remains with a great importance to prevent its further progression and increase survival rates. Colonoscopy and pathological examinations which are invasive and painful procedures, are needed to make a definitive diagnosis of CRC. The carcinoembryonic antigen CEA is particularly used for postoperative follow-up of CRC patients. The imbalance between matrix metalloproteinases MMPs and their tissue inhibitors of metalloproteinases TIMPs leads to degradation of extracellular matrix which is the most important step in invasion and metastasis. It was also observed that cyclooxygenase-2 COX-2 has crucial roles in the development and progression of colorectal cancer. The purpose of our study is to detect fecal and plasma MMP-7, COX-2, TIMP-1, and CEA protein levels in patients with colorectal cancer, colorectal polyps, and healthy individuals, and assess their association with each other and with clinicopathological variables. We also aimed to evaluate plasma and fecal MMP-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-three healthy volunteers. Protein extraction was carried out from fecal samples. Plasma and fecal MMP-7, TIMP-1, and COX-2 protein levels were determined 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 were significantly elevated in cancer according to polyp group. We also detected decreased plasma MMP-7 levels in polyps compared to control group. 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 CRC from 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 differentiate CRC 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 of colorectal adenocarcinoma. In addition, plasma CEA and TIMP-1 are also valuable biomarker candidates in differentiating colorectal cancer from colorectal polyps

Keywords:

Colorectal cancer, colorectal polyps, tissue inhibitors of metalloproteinases-1, matrix metalloproteinase-7, cyclooxygenase-2, carcinoembryonic antigen,

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