Predictive value of tissue inhibitor of metalloproteinases-1 and carcinoembryonic antigen plasma levels in response to chemotherapy in patients with metastatic colorectal cancer

Abstract

Background: Colorectal cancer is one of the most important causes of morbidity and mortality in the world. It has been suggested that tissue inhibitor of metalloproteinase-1 (TIMP-1) plays a particular role in cancer promotion. The objective of the present study was to compare the effect of repeated measurement of carcinoembryonic antigen (CEA) and TIMP-1 plasma levels in a follow-up response to chemotherapy treatment in patients with unresectable metastatic colorectal cancer by surgery. Materials and Methods: All consecutive patients between 18 and 75 years old in both genders with rectal adenocarcinoma who referred to Sayed Al-Shohada Medical Center, during 6 months of study period enrolled in the study. Level of CEA and TIMP-1 were assessed before and after two cycles of chemotherapy. Furthermore, patients underwent computed tomography scan to assess response to chemotherapy. The sensitivity, specificity, and areas under the receiver operating characteristic curves (AUC) calculated for baseline level of CEA and TIMP. Results: The mean age of the studied patients was 52.7 } 7.5 years, 12 patients (48%) were male. Response to chemotherapy after two cycles was 80%. In patients who responded to chemotherapy level of TIMP after treatment was significantly decreased compared to before treatment (P < 0.0001). Before and after treatment in patients who responded to chemotherapy the level of TIMP was significantly lower than who did not response to chemotherapy (P < 0.05). The critical values for the prediction response to chemotherapy for CEA was >63 (AUC: 0.54) and for TIMP was ?8823 (AUC: 0.68). Conclusion: The present study has identified a strong significant association between high plasma TIMP-1 levels and short survival in patients with colorectal cancer. In addition, results demonstrated that the TIMP-1 provides stronger prognostic information than CEA.

Key words: Carcinoembryonic antigen, chemotherapy, metastatic colorectal cancer, predictive value, tissue inhibitor of metalloproteinase-1