Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis

Abstract

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.

<p>Matrilysins and Stromelysins in Pathogenesis and Diagnostics of Cancers</p>

“…Disturbances in expression and activation of matrilysins and stromelysins often results in the development of inflammation and in consequence dysplastic changes in cells, and even cancer transformation. Our research team over the last years carefully investigated various MMPs in gynaecologic malignancies, e.g., ovarian cancer, 109 , 110 cervical cancer 111 , 112 and BC. 113 , 114 Our data, indicated that MMPs had a diagnostic utility in gynaecologic cancers, also a wide scientific literature seems to confirmed this reports.…”

Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances

“…This study indicates that MMP-9 expression in cervical cancer is an independent prognostic factor. In several other studies, MMP-9 level in plasma was measured and compared between patient group and control groups using enzyme-linked immunosorbent assay (ELISA) [ 94 , 95 , 96 ]. These studies found that MMP-9 could be a useful biomarker in the diagnosis of cervical cancer in combination with other biomarkers.…”

Molecular Imaging Probes Based on Matrix Metalloproteinase Inhibitors (MMPIs)

“…This makes MMP-9 a preferential candidate for the early detection of these types of tumors. The elevated MMP-9 expression in those tumors compared with healthy controls can be detected due to the recent development of experimental analytical techniques such as proteomic analysis, immunohistochemical studies, immunochemistry assays and tandem mass spectrometry [29,30,31]. The augmented levels of MMP-9 can be detected in plasma or blood samples, showing triple protein levels compared to healthy patients.…”

“…The augmented levels of MMP-9 can be detected in plasma or blood samples, showing triple protein levels compared to healthy patients. The study carried out by Zajkowska et al [29] showed that patients with cervical cancer in stages III and IV present MMP-9 plasma levels of 3344.44 ng/mL and 325.80 ng/mL, respectively, with almost three times more compared to healthy patients which present with normal levels of 166.00 ng/mL. De Chiara et al [32] measured the MMP-9 levels in blood samples and found them to be triple (302.92 ng/mL) for NSCLC patients than in healthy controls (136.14 ng/mL).…”