Sławomir Ławicki

The plasma concentration of VEGF, HE4 and CA125 as a new biomarkers panel in different stages and sub-types of epithelial ovarian tumors

BackgroundVEGF may play a role in the pathogenesis of cancer disease, for example in cell growth, proliferation and angiogenesis. In this study, we investigated plasma levels of this cytokine in comparison to plasma levels of a new biomarker - HE4 and the established tumor marker CA125 in ovarian cancer patients (100) as compared to control groups: patients with a benign ovarian tumor (80) and healthy subjects (50).MethodsPlasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method.ResultsThe results showed that levels of VEGF, CA125 and HE4 were significantly higher in ovarian cancer (OC) patients as compared to the both control groups. VEGF has demonstrated as high as comparative markers values of the diagnostic sensitivity (SE), specificity (SP), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in early stages of cancer tested groups. The combined use of parameters studied resulted in the increase in the diagnostic criteria values and the AUC.ConclusionsThese findings suggest the usefulness of VEGF in the early diagnostics of ovarian cancer, especially in combination with CA125 and HE4, as a new biomarkers panel. Additionally, VEGF is the most useful tool in the diagnostics of locally advanced ovarian cancer without metastases. Investigated cytokine presented similar to HE4 usefulness in differentiation of OC according to its histopathlogical sub-type, and could be used especially in the diagnostics of endometrioid epithelial OC.

Hematopoietic cytokines as tumor markers in gynecological malignancies. A multivariate analysis in epithelial ovarian cancer patients

We investigated plasma levels of selected hematopoietic cytokines: stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) and the tumor marker cancer antigen (CA 125) in epithelial ovarian cancer patients as compared with control groups: benign ovarian tumor patients (cysts) and healthy subjects. Cytokine levels were determined by enzyme-linked immunosorbent assay, CA 125 – using the chemiluminescent microparticle immunoassay method. Our results have demonstrated significant differences in the concentrations of M-CSF, G-CSF, SCF (with the exception of GM-CSF), and CA 125 between the groups of ovarian cancer patients, cysts patients, and the healthy controls. When compared with CA 125, M-CSF has equal or higher values of diagnostic sensitivity and specificity. The M-CSF area under the receiver-operating characteristic curve (AUC) was the largest from all the cytokines tested and slightly lower than the AUC of CA 125. These findings suggest the usefulness of M-CSF in diagnosing ovarian cancer, especially when discriminating between cancer and non-carcinoma lesions.

Hematopoietic cytokines as tumor markers in gynecological malignancies: a multivariate analysis with ROC curve in endometrial cancer patients.

Hematopoietic cytokines have been implicated in the pathogenesis of malignant diseases. This study compared the diagnostic utility of hematopoietic growth factors with commonly accepted tumor marker (CA 125) in the early stages (I and II) of endometrial cancer (EC) patients (65) in relation to the control groups: uterine myoma patients (40) and healthy subjects (45). The pretreatment plasma levels of interleukin 3, stem cell factor, granulocyte-macrophage-colony stimulating factor, granulocyte-colony stimulating factor, and macrophage-colony stimulating factor (M-CSF) were determined by the use of immunoenzyme assay, and those of CA 125 were determined by chemiluminescent microparticle immunoassay. Our results have demonstrated significant differences in the concentration of cytokines and CA 125 between the groups of EC patients, uterine myoma patients, and the healthy controls. M-CSF has demonstrated equal to CA 125 or higher values of the diagnostic sensitivity, the predictive values of positive and negative test results, and the area under the receiver-operating characteristics curve in the tested groups. These findings suggest the usefulness of M-CSF in the diagnosis of EC and uterine myomas.

Plasma levels and diagnostic utility of VEGF, MMP-9, and TIMP-1 in the diagnosis of patients with breast cancer.

Vascular endothelial growth factor (VEGF), matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 may play a role in the pathogenesis of cancer disease. We investigated their levels and utility in comparison to cancer antigen (CA) 15-3 in patients with breast cancer (BC) and in relation to the control groups. The study included 100 women with BC, 50 patients with benign breast tumor, and 50 healthy women. The plasma levels of the tested parameters were determined using enzyme-linked immunosorbent assay, while CA 15-3 with chemiluminescent microparticle immunoassay. The results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between groups of patients with BC and healthy patients or patients with benign breast tumor. The plasma levels of VEGF and tissue inhibitor of metalloproteinase-1 were significantly higher in advanced tumor stages. The tested parameters were comparable to CA 15-3 values of the diagnostic sensitivity, specificity, the predictive values of positive and negative test results, and the area under the receiver-operating characteristic curve. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, negative predictive value, and area under the receiver-operating characteristic curve, especially in the combination of VEGF with tumor marker (84%, 73%, 0.888, respectively). These findings suggest the usefulness of the tested parameters in the diagnosis of BC. VEGF, especially in combination with CA 15-3, showed the highest usefulness in the diagnosis of early BC.

VEGF, M-CSF and CA 15-3 as a new tumor marker panel in breast malignancies: a multivariate analysis with ROC curve

Abstract The plasma levels of Vascular endothelial growth factor, macrophage-colony stimulating factor (M-CSF) and CA15-3 in breast cancer patients (BC) were investigated and compared with control groups: benign breast tumor patients and the healthy subjects. Cytokine levels were determined by the use of enzyme-linked immunosorbent assay, CA 15-3 - by chemiluminescent microparticle immunoassay method. Our results have demonstrated significant differences in the concentration of cytokines and CA 15-3 between the groups of BC patients and two control groups. Cytokines have demonstrated equal to CA 15-3 or even higher values of the diagnostic sensitivity (SE), the predictive values of positive and negative test results (PV-PR, PV-NR), and the area under the ROC curve (AUC) in the studied groups. The combined use of tested parameters resulted in the increase of the SE, PV-PR and AUC. These findings suggest the usefulness of both cytokines in the diagnosis of BC, but only M-CSF in discrimination between cancer and non-carcinoma lesions, especially in combination with CA 15-3.

M-CSF in a new biomarker panel with HE4 and CA 125 in the diagnostics of epithelial ovarian cancer patients

BackgroundWe investigated plasma levels of M-CSF and conventional tumor markers (HE4 and CA 125) in epithelial ovarian cancer patients as compared to control groups: benign ovarian tumor patients (cysts) and healthy subjects.MethodsM-CSF levels were determined by ELISA, HE4 and CA 125 levels - by CMIA method.ResultsOur results have demonstrated significant differences in the concentration levels of M-CSF, CA 125 and HE4 between the groups of ovarian cancer patients, cysts patients and the healthy controls. In the groups tested M-CSF demonstrated equal to or higher values than both CA 125 and HE4 in diagnostic sensitivity (SE), positive and negative predictive values (PPV, NPV), and in the area under the ROC curve (AUC), particularly in the group with the serous epithelial sub-type of OC. Moreover, CA 125 showed better results of the aforementioned diagnostic criteria than HE4. The combined use of the parameters studied resulted in a further, significant increase in the value of the diagnostic indicators and in the value of the diagnostic power (AUC), especially in the early stages of ovarian cancer.ConclusionsThese findings suggest a high usefulness of M-CSF in diagnosing the serous sub-type of epithelial ovarian cancer and in discriminating between cancer and non-carcinoma lesions, particularly in new diagnostic panels in combination with CA 125 and HE4 for the detection of EOC in the early stages.

Pretreatment plasma levels and diagnostic utility of hematopoietic cytokines in cervical cancer or cervical intraepithelial neoplasia patients

In this study, we compared plasma levels and the diagnostic utility of hematopoietic growth factors (HGFs) with SCC-Ag in cervical cancer patients in relation to control groups and cervical intraepithelial neoplasia (CIN) patients and healthy subjects. Pretreatment plasma levels of HGFs (SCF, GM-CSF, G-CSF and M-CSF) were determined by the use of immunoenzyme assay (ELISA), and SCC-Ag by chemiluminescent microparticle immunoassay (CMIA). Significantly different concentrations of GM-CSF, G-CSF and M-CSF were observed in the group of patients with cervical cancer and CIN compared to the healthy controls. Significant differences in plasma levels of GM-CSF and M-CSF between cervical cancer and benign lesions patients were also found. The HGFs and SCC-Ag diagnostic specificities received high values. The diagnostic sensitivity and the predictive value of a positive and negative test result were higher for M-CSF than for antigen SCC in the cancer group. The M-CSF area under the ROC curve (AUC) was the largest from hematopoietic cytokines and SCC-Ag. These results suggest the potential utility of M-CSF as a good candidate for a marker of cervical cancer as well as benign lesions of this organ (CIN).

Diagnostic Power of Vascular Endothelial Growth Factor and Macrophage Colony-Stimulating Factor in Breast Cancer Patients Based on ROC Analysis

Breast cancer (BC) is the most common malignancy in women. Vascular endothelial growth factor (VEGF) has been described as an important regulator of angiogenesis which plays a vital role in the progression of tumor. Macrophage colony-stimulating factor (M-CSF) is a cytokine whose functions include regulation of hematopoietic lineages cells growth, proliferation, and differentiation. We investigated the diagnostic significance of these parameters in comparison to CA15-3 in BC patients and in relation to the control group (benign breast tumor and healthy women). Plasma levels of the tested parameters were determined by ELISA and CA15-3 was determined by CMIA. VEGF was shown to be comparable to CA15-3 values of sensitivity in BC group and, what is more important, higher values in early stages of BC. VEGF was also the only parameter which has statistically significant AUC in all stages of cancer. M-CSF has been shown to be comparable to CA15-3 and VEGF, specificity, and AUC values only in stages III and IV of BC. These results indicate the usefulness and high diagnostic power of VEGF in the detection of BC. Also, it occurred to be the best candidate for cancer diagnostics in stages I and II of BC and in the differentiation between BC and benign cases.

Plasma Levels and Diagnostic Utility of Macrophage Colony-Stimulating Factor, Matrix Metalloproteinase-9, and Tissue Inhibitor of Metalloproteinases-1 as New Biomarkers of Breast Cancer

Background Macrophage colony-stimulating factor (M-CSF), matrix metalloproteinase-9 (MMP-9), and its specific tissue inhibitor - tissue inhibitor of metalloproteinases-1 (TIMP-1) may play an important role in the pathogenesis and spread of cancer. We investigated the plasma levels of M-CSF, MMP-9, and TIMP-1 in comparison with a commonly accepted tumor marker CA 15-3 in breast cancer patients and in control groups. Methods The cohort included 110 breast cancer patients in groups at stages I-IV. The control group consisted of 50 healthy volunteers and 50 benign tumor patients. Plasma levels of M-CSF, MMP-9, and TIMP-1 were determined by using ELISA, while CA 15-3 concentrations were determined by using chemiluminescent microparticle immunoassay (CMIA). Results The results showed significant differences in concentrations of the analyzed parameters and in levels of CA 15-3 between the groups of breast cancer patients and the two control groups. Diagnosis using these markers was equal to that using CA 15-3 in terms of sensitivity, predictive values of positive and negativetest results (PPV, NPV) and area under the ROC curve (AUC) in the studied groups. The diagnostic specificities of MMP-9, TIMP-1, M-CSF, and CA 15-3 showed equally high values (95%). The combined use of all tested parameters with CA 15-3 resulted in increased sensitivity, NPV, and AUC, especially in the combination of M-CSF with tumor markers (76%, 64%, and 0.8653). Conclusions These findings suggest the tested parameters are useful in the diagnosis of breast cancer patients (except stage I), when combined with CA 15-3.

Hematopoietic cytokines as tumor markers in breast malignancies. A multivariate analysis with ROC curve in breast cancer patients

PURPOSE Plasma levels of selected hematopoietic cytokines: interleukin 3 ( IL-3), stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF), and the tumor marker carcinoma antigen 15-3 (CA 15-3) in breast cancer (BC) patients were investigated and compared to control groups: benign breast tumor patients and healthy subjects. MATERIAL/METHODS Cytokine levels were determined by ELISA, CA 15-3 - using the CMIA method. RESULTS A significant differences in the concentration of cytokines (with the exception of IL-3) and CA15-3 between the groups of BC patients, benign breast tumor patients and the healthy controls have been demonstrated. M-CSF has demonstrated higher or equal to CA 15-3 values of diagnostic sensitivity, specificity and the predictive values of positive and negative test results. The M-CSF area under the ROC curve (AUC) was the largest from all the cytokines tested and marginally lower than the AUC of CA 15-3. CONCLUSION These findings suggest the usefulness of M-CSF in diagnosing breast cancer, especially when discriminating between cancer and non-carcinoma lesions.