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.
Highlights
Cancer of the uterine cervix is the leading cause of death among gynecological cancers in developing countries and the fourth principal cause of cancer-related death in women worldwide [1]
The median value of Tissue inhibitor of metalloproteinase-2 (TIMP-2) (76.00 ng/mL) in the total cervical cancer group was significantly lower compared with the values in healthy subjects (87.25 ng/mL) (p < 0.05)
Our results show that the diagnostic power (AUC) of the tested parameters, especially Macrophage colony-stimulating factor (M-CSF), in the group of CC patients was marginally lower in comparison with the diagnostic power of M-CSF in the course of pancreatic cancer study conducted by Vasiliades et al [34]
Summary
Cancer of the uterine cervix is the leading cause of death among gynecological cancers in developing countries and the fourth principal cause of cancer-related death in women worldwide [1]. High-risk human papillomavirus (HPV) infection is considered the most important risk factor associated with the development of this tumor, and it is present in 99.7% of invasive cervical tumors worldwide including essentially all squamous cell cancers and adenocarcinomas [2]
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