Diagnostic Power of Cytokine M-CSF, Metalloproteinase 2 (MMP-2) and Tissue Inhibitor-2 (TIMP-2) in Cervical Cancer Patients Based on ROC Analysis

Abstract

Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-2 (MMP-2) and its specific tissue inhibitor (TIMP-2) may play an important role in the pathogenesis of cancer disease. We investigated the plasma levels and diagnostic power (ROC curve analysis) of M-CSF, MMP-2, TIMP-2 and tumor markers CA 125 and SCC-Ag in cervical cancer (CC) patients as compared to control group. The study included 89 patients with cervical cancer. The control group consisted of 50 healthy, untreated women. The plasma levels of M-CSF, MMP-2 and TIMP-2 were determined using ELISA, CA 125 and SCC-Ag – by CMIA method. The median levels of M-CSF, TIMP-2, SCC-Ag and CA 125 in the entire group of CC were significantly different than compared to the healthy women group. MMP-2 showed the highest value of sensitivity from all examined parameters (in stage I of CC – 93.10%, II – 82.76%, III and IV – 96.88%, total group – 92.05%). The highest specificity was obtained by M-CSF (86%). The area under the ROC curve (AUC) of M-CSF (0.8051) was the largest of all the tested parameters (even higher than commonly used tumor markers) in the group of cervical cancer. The combination of M-CSF, MMP-2 or TIMP-2 with SCC antigen resulted in an increase AUCs in all cases (0.8760;0.7880;0.8081;respectively). The findings of this study suggest the usefulness of all examined parameters in the diagnostics of CC patients. Out of the tested substances, M-CSF also appears to be the best candidate for cancer diagnostics in all stages of the disease, based on ROC analysis.