Crosstalk of Immune Cells and Platelets in an Ovarian Cancer Microenvironment and Their Prognostic Significance.

Ovarian cancer (OC) is one of the deadliest gynecological cancers, largely due to the fast development of metastasis and drug resistance. The immune system is a critical component of the OC tumor microenvironment (TME) and immune cells such as T cells, NK cells, and dendritic cells (DC) play a key role in anti-tumor immunity. However, OC tumor cells are well known for evading immune surveillance by modulating the immune response through various mechanisms. Recruiting immune-suppressive cells such as regulatory T cells (Treg cells), macrophages, or myeloid-derived suppressor cells (MDSC) inhibit the anti-tumor immune response and promote the development and progression of OC. Platelets are also involved in immune evasion by interaction with tumor cells or through the secretion of a variety of growth factors and cytokines to promote tumor growth and angiogenesis. In this review, we discuss the role and contribution of immune cells and platelets in TME. Furthermore, we discuss their potential prognostic significance to help in the early detection of OC and to predict disease outcome.

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.

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.

Plasma levels and diagnostic utility of VEGF, MMP-2 and TIMP-2 in the diagnostics of breast cancer patients.

OBJECTIVE: We investigated plasma levels and diagnostic utility of vascular endothelial growth factor VEGF, matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2) in comparison to cancer antigen 15-3 (CA 15-3). METHODS: Plasma levels of tested parameters were determined using enzyme-linked immunosorbent assay (ELISA) while CA 15-3 with chemiluminescent microparticle immunoassay (CMIA). RESULTS: The plasma levels of VEGF, TIMP-2 showed significantly higher than CA 15-3 values of the diagnostic sensitivity, the predictive values of positive and negative test results (PPV, NPV) and the area under the receiver-operating characteristics (ROC) curve (AUC) in early stages of breast cancer (BC). The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, NPV and AUC, especially in the combination with VEGF (83%; 72%; 0.888) and TIMP-2 (83%; 72%; 0.894). The highest values were obtained for combination of all three parameters (93%; 85%; 0.923). CONCLUSIONS: These findings suggest the usefulness of the tested parameters in the diagnosis of BC, especially VEGF and TIMP-2 with CA 15-3 in early stages of BC, which could be a new diagnostic panel.

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.

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

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.

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.

[The plasma levels and diagnostic utility of selected hematopoietic growth factors in endometrial cancer patients and with myoma uteri]. / Ocena stezenia i przydatnosci diagnostycznej wybranych cytokin hematopoetycznych w osoczu chorych na raka endometrium i ze zmianami lagodnymi (miesniakami) macicy.

UNLABELLED: Hematopoietic growth factors (HGFs) are involved in the regulation of growth hematopoietic cells. Some clinical investigations have shown an autologous production of HGFs in various human cell lines in vitro and by tumour cells in vivo, for example in endometrial cancer. THE AIM OF THE STUDY: To evaluate the plasma levels and diagnostics utility of selected HGFs, such as SCF M-CSF, G-CSF in endometrial cancer patients and with myoma uteri. MATERIAL AND METHODS: We have investigated the plasma levels of HGFs and tumor marker like CA 125 in patients with endometrial cancer (55 women), with myoma uteri (30 patients) and in 30 healthy subjects. HGFs were determined using enzyme-linked immunosorbent assay (ELISA), CA 125 was measured by chemiluminescence immunoassay (CMIA). RESULTS: SCF and M-CSF similarly to CA 125 plasma levels were significantly higher in endometrial cancer patients comparing to the healthy subjects. Furthermore M-CSF was significantly higher in endometrial cancer comparing to the myoma patients. The diagnostic sensitivity of M-CSF was high and slightly lower than CA 125 (51% and 60% respectively). The combined use of all tested cytokines resulted in the increased sensitivity range, especially with marker CA 125 (84%). Diagnostic specificities were high and equal for all tested cytokines and for CA 125(93%). Positive predictive values (PPV) were high for all tested parameters, and negative predictive values (NPV) were higher enough to exclude endometrial cancer. CONCLUSIONS: Our study suggest that tested cytokines (HGFs) can be clinically useful in diagnostic of endometrial cancer patients. M-CSF can be clinically useful in differentiation of endometrial cancer and myoma uteri. Furthermore SCF and M-CSF showed usefulness in primary diagnostic of cancer uteri, especially with CA 125.

[Molecular markers of carcinogenesis in the diagnostics of cervical cancer]. / Molekularne markery karcynogenezy w diagnostyce raka szyjki macicy.

Cervical carcinoma is the most frequent disease of the reproductive organ and is the second most common cancer in women after breast cancer. As it is characterized by high mortality, new diagnostic methods are needed, for example tumor markers, enabling earlier diagnosis and rapid detection of recurrence after therapy. Different tumor markers may be useful in the diagnostics of cervical cancer, for example squamous cell carcinoma antigen (SCC-Ag), tissue polypeptide antigen (TPA), and CYFRA 21-1, as well as some cytokines such as vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor, and macrophage colony-stimulating factor (M-CSF). About 150 genes connected with the carcinogenesis of cervical carcinoma have been identified. This paper is devoted to evaluating the diagnostic usefulness of molecular markers of carcinogenesis, especially P53, Bcl-2, Brn-3a, and MCM, and comparing the results with those of typical tumor markers or cytokines useful in diagnosing this type of cancer. It was shown that telomerase and Brn-3a proteins demonstrate usefulness in screening examination, P53 in monitoring the effectiveness of therapy, and Bcl-2 as a survival prognostic factor. In summary, it is evident that molecular makers of carcinogenesis are helpful in the diagnostics of cervical cancer, but further investigation and confirmation by a prospective study is necessary.

[The plasma levels and diagnostic utility of stem cell factor in patients with endometrial cancer and myoma uteri]. / Ocena stezenia i przydatnosci diagnostycznej czynnika wzrostu komórek pnia w osoczu chorych na raka endometrium oraz ze zmianami lagodnymi (miesniakami) macicy.

UNLABELLED: Stem cell factor (SCF) is a member of a group of cytokines called hematopoietic growth factors (HGFs). Some clinical investigations have shown an autologous production of this cytokine in various human cell lines in vitro and by tumors in vivo, for example in uterine cancer. THE AIM OF THE STUDY: The plasma level and diagnostic utility of SCF have been investigated in endometrial cancer and myoma patients. MATERIAL AND METHODS: The plasma level of SCF and tumor markers like CA 125 and SCC-Ag in endometrial cancer (50 patients), in myoma uteri (25 patients) and in 25 healthy subjects were determined using enzyme-linked immunosorbent assay (ELISA) and chemiluminescence immunoassay (CMIA). RESULTS: SCF plasma level was significantly higher in endometrial cancer patients comparing to the group with myoma and to the control. CA 125 plasma level was significantly higher only in endometrial cancer patients comparing to the control group. Diagnostic specificity was high and equal for all tested parameters (92%). The diagnostic sensitivity of SCF was slightly lower than CA 125, and was higher in more advanced tumor stage. The combined use of SCF with other markers resulted in the increased sensitivity range. Positive and negative predictive values were high for SCF and for CA 125, and were higher in more advanced tumor stage. CONCLUSIONS: Our study suggests that tested cytokine (SCF) can be clinically useful in differentiation of endometrial cancer and myoma uteri. Furthermore SCF showed usefulness in primary diagnostic of cancer uteri, especially with CA 125.

Diagnostic Power of Selected Cytokines, MMPs and TIMPs in Ovarian Cancer Patients - ROC Analysis.

BACKGROUND/AIM: The aim of the study was to identify new non-invasive ovarian cancer (OC) tumor markers. MATERIALS AND METHODS: In postmenopausal ovarian cancer patients and in a control group (benign ovarian lesions and healthy subjects), preoperative plasma levels of cytokines, metalloproteinases and their tissue inhibitors were determined using ELISA while those of CA125 and HE4 by chemiluminescent microparticle immunoassay methods. RESULTS: The diagnostic sensitivity (SE) value was the highest for HE4 and MMP-7 (78.0%). The diagnostic specificity (SP) for M-CSF, VEGF and MMP-9 was 95.2%, 95.2% and 95.7%, respectively. The highest positive predictive value (PPV) for M-CSF and MMP-9 was ~84.6% and negative predictive value (NPV) for MMP-7 and HE4 was ~87.6%. The biggest areas under the ROC curve were obtained for the combination of VEGF, MMP-7 or MMP-9 with HE4+CA125 (0.9130-0.9234), but not for CA125+HE4 (0.8260). CONCLUSION: Our research confirms the validity of combining classic markers with new markers to improve the diagnostic power of CA125 and HE4.

[Tumor markers useful in the diagnostics and monitoring of endometrial and cervical cancer]. / Markery nowotworowe przydatne w diagnostyce i monitorowaniu raka endometrium i szyjki macicy.

Tumor markers play an important role in the diagnosis of cancer. Cervical carcinoma and endometrial cancer are the most frequent diseases of the reproductive organs and their morbidity rates are constantly increasing. Many tumor markers may be used in the diagnosis and monitoring of endometrial and cervical carcinoma, for example CA 125, SCC-Ag, TPA, TPS, and CYFRA 21-1. New tumor markers useful in the early diagnosis and in monitoring the treatment and recurrence of the uterine cancer are still being sought. Investigations are underway on such substances as cytokines (e.g. M-CSF) and molecular markers of carcinogenesis (e.g. K-ras and p53).

[New tumour markers useful in diagnostics and monitoring of cervical cancer]. / Nowe markery nowotworowe przydatne w diagnostyce i monitorowaniu raka szyjki macicy.

Cervical carcinoma is the most frequent disease of the female reproductive organs. The tumour markers may be helpful: in early diagnosis of cervical cancer, the initial assesment of the extent of the disease, monitoring of tumour growth or tumour volume reduction, recurrence of cancer, and have been used for monitoring of the clinical course of chemotherapy and radiotherapy. In this paper we have focused on the role of new tumour markers, especially cytokines (for example G-CSF, VEGF) and molecular markers of carcinogenesis (for example Bcl-2 and p53), in comparison to typical tumour markers useful in diagnostic of cervical cancer such as CA 125, SCC-Ag, TPA, TPS, CYFRA 21-1.

Narrowband ultraviolet B light treatment changes plasma concentrations of MMP-3, MMP-9 and TIMP-3 in psoriatic patients.

BACKGROUND: Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are thought to be associated with the pathogenesis and spread of psoriatic disease. This study was designed to investigate the plasma levels of MMP-3, MMP-9 and TIMP-3 in plaque psoriasis patients prior to and following a course of ultraviolet B narrowband treatment with respect to disease advancement. METHODS: Plasma samples of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were evaluated. Concentrations of MMP-3, MMP-9 and TIMP-3 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index was used to define disease advancement. RESULTS: Plasma levels of MMP-3, MMP-9 and TIMP-3 were significantly elevated in psoriasis patients compared to healthy individuals. A course of ultraviolet B narrowband treatment resulted in a significant decline in the studied metalloproteinases. Furthermore, the concentration of selected tissue inhibitors was negatively correlated with baseline Psoriasis Area and Severity Index score. CONCLUSION: Our research highlights the meaningful role of MMP-3, MMP-9 and TIMP-3 in psoriasis pathogenesis and clearance of disease symptoms. Furthermore, plasma levels of the analyzed metalloproteinases seem to be a valuable psoriasis biomarker.

Plasma levels of MMP-7 and TIMP-1 in laboratory diagnostics and differentiation of selected histological types of epithelial ovarian cancers.

BACKGROUND: MMP-7 and TIMP-1 may play a role in the pathogenesis of cancer disease. In this study we investigated plasma levels of selected metalloproteinase and its tissue inhibitor in comparison to plasma levels of the commonly accepted tumor markers (CA 125 and HE4) in selected histological types of epithelial ovarian cancer patients as compared to control groups: patients with a benign ovarian tumor and healthy subjects. Plasma levels of MMP-7 and TIMP-1 were determined using ELISA, CA 125 and HE4 - by CMIA methods. RESULTS: Plasma levels of all biomarkers studied were significantly higher in ovarian cancer patients as compared to both control groups. MMP-7 demonstrated comparable to HE4 or CA125 values of diagnostic sensitivity (SE: 61%; 68%; 58%, respectively), specificity (SP: 95%; 95%; 98%, respectively), positive (PPV: 93%; 96%; 98%, respectively) and negative predictive values (NPV: 61%; 66%; 60%, respectively) in the groups tested. The combined use of the aforementioned biomarkers resulted in a further increase in diagnostic criteria and AUC, especially in the early stages of the disease. CONCLUSIONS: These findings suggest the usefulness of combining MMP-7 with CA 125 and HE4 in the diagnosis of epithelial ovarian cancer as a new tumor marker panel.

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.

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.

Therapy of psoriasis with narrowband ultraviolet-B light influences plasma concentrations of MMP-2 and TIMP-2 in patients.

BACKGROUND: Matrix metalloproteinases (MMPs), which show a significant ability to cleave the components of extracellular matrix, and tissue inhibitors of metalloproteinases (TIMPs), which slow down the activity of those enzymes, may be implicated in the pathogenesis and spread of psoriatic disease. This study aims to analyze plasma levels of MMP-2 and TIMP-2 in plaque psoriasis patients before and after the course of narrowband ultraviolet-B (NBUVB) therapy with respect to disease advancement. PATIENTS AND METHODS: A total of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were enrolled into the study. Plasma levels of MMP-2 and TIMP-2 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index (PASI) was used to define the disease advancement. RESULTS: The results showed increased plasma levels of MMP-2 and TIMP-2, but this change was significant only in case of MMP-2 in total psoriatic group compared to healthy subjects. Moreover, there was an increase in the concentrations of chosen factors with an increase in the severity of the disease. The NBUVB therapy causes a decline in the concentration of the analyzed enzyme and its inhibitor, although this change was statistically significant in the total psoriatic group only in case of MMP-2. There was also a positive correlation between MMP-2, TIMP-2, and PASI score value. CONCLUSION: Our study highlights a possible important role of MMP-2 in the activity of psoriasis and clearance of disease symptoms. Moreover, plasma MMP-2 seems to be a valuable psoriasis biomarker.

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

BACKGROUND: We 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. METHODS: M-CSF levels were determined by ELISA, HE4 and CA 125 levels - by CMIA method. RESULTS: Our 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. CONCLUSIONS: These 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.

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

BACKGROUND: VEGF 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). METHODS: Plasma levels of VEGF were determined by ELISA, HE4 and CA125 by CMIA method. RESULTS: The 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. CONCLUSIONS: These 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.