Objectives: Cytokines are potential new serum markers, especially desirable for malignancies with poor prognosis like non-small cell lung cancer (NSCLC). Methods: Cytokines, tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-8, soluble TNF (sTNF) RI, sTNF RII, soluble IL-2 receptor-α, IL-1 receptor antagonist (IL-1ra), IL-10, vascular endothelial growth factor, basic fibroblast growth factor, and macrophage (M-CSF) and granulocyte colony-stimulating factor, as well as tumor markers – carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and CYFRA 21.1 – were assessed in the sera of 103 untreated NSCLC patients, and these cytokines and tumor markers were refered to clinical parameters of the disease and to the overall survival of patients evaluated during a 6-year follow-up. Results: Most of the factors analyzed were found to be elevated in the sera of NSCLC patients, and increases in IL-6, IL-8 and sTNF RI were noted in the greatest proportion of stage I patients. Most cytokine/cytokine receptor levels revealed higher sensitivity than the standard tumor markers; IL-6 and IL-1ra levels were significantly different in patients with squamous cell versus adenocarcinoma; IL-6 and IL-10 were related to the tumor size, while IL-6 and M-CSF levels significantly increased with disease progression. A significant prognostic value of pretreatment serum M-CSF and CEA levels in NSCLC patients has been shown, but only M-CSF proved to be an independent prognostic factor. Conclusions: Increased pretreatment serum M-CSF level is a significant independent predictor of poor survival in patients with NSCLC.

The aim of this study is to determine the prognostic value of tumor markers, as squamous cell carcinoma antigen (SCCAg) and cytokeratin-19 fragment (CYFRA 21.1) and interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), soluble tumor necrosis factor receptor I (sTNF RI), and sTNF RII in patients with squamous cell carcinoma of the cervix. The subjects of analysis were 138 patients with stage I–IVA according to the International Federation of Gynecology and Obstetrics (FIGO) classification. The collected research material comes from one oncology center. During the 10 years of follow-up, 56 relapses and 53 deaths were observed, and recurrent disease in early stage was confirmed in 45 % of patients. The pretreatment serum levels of SCCAg and CYFRA 21.1, and cytokines IL-6, VEGF, sTNF RI, and sTNF RII were determined in all patients. The probability of disease-free survival (DFS) and overall survival (OS) was evaluated using the log-rank test and the Cox regression model. Based on the ROC curve analysis for patients with recurrence, the largest area under the curve was demonstrated for SCCAg and IL-6 and for patients who died, for SCCAg and VEGF. Cox analysis demonstrated that independent prognostic factor for DFS was only SCCAg and for OS cytokine IL-6 and SCCAg, but in patients with early stage the prognostic value for DFS was VEGF, whereas IL-6 and CYFRA 21.1 for OS. Serum level of VEGF, CYFRA 21.1 and IL-6 before treatment in patients with early stage cervical cancer appears to be an important prognostic factor.

ObjectivesThe study aimed to assess the usefulness of the determination of cytokines: IL-8, VEGF and its soluble receptors: VEGF-R1, VEGF-R2 in patients with endometrial cancer (EC).Material/MethodsThe study group consisted of 118 patients with EC subjected to surgical treatment. Before the treatment we determined the serum levels of cytokines IL-8, and VEGF as well as VEGFR1 and VEGFR2 receptors. For comparison, the concentration of CA 125 was also measured. VEGFR1 and CA 125 were determined in the COBAS e601 system using Roche Diagnostics kits, while IL-8, VEGF and VEGFR2 were measured by ELISA assay using R&D Systems kits.ResultsThe concentrations of IL-8, VEGF, VEGFR1 and CA 125 allowed to distinguish patients for the control group. The highest diagnostic sensitivity has been shown for the concentrations of VEGF (AUC = 0.904) and IL-8 (AUC = 0.818). Among all studied parameters only CA125 concentrations increased with the clinical stage; being significantly higher in patients in FIGO III-IV, than FIGO I-IB. In patients at the FIGO stage I-IB, complementary determinations of CA 125 and VEGF resulted in the largest increase of diagnostic sensitivity. Patients with metastases to the para-aortic lymph nodes had significantly higher levels of VEGF compared to subjects without such lesions. The concentrations of IL-8 were an independent prognostic factor in the assessment of overall survival in patients with type I endometrial cancer, while the concentrations of VEGFR2 in those with type II.ConclusionsIn patients with endometrial cancer, the clinical usefulness of IL-8 and VEGFR2 measurements as the potential prognostic factors has been demonstrated. In type I, the concentrations of IL-8 determined before treatment can be helpful in predicting overall survival. In patients qualified to type II EC, the concentrations of VEGFR2 have the value of an independent prognostic factor for overall survival, this requires research on larger groups of patients. The increased levels of VEGF may be useful in the preoperative assessment of the status of para-aortic lymph nodes.

ObjectiveOur study assessed the clinical utility and prognostic value of pretreatment hematological parameters and calculated coefficients including the platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), and monocyte to lymphocyte ratio (MLR) in patients with cervical adenocarcinoma (CA).Materials and methodsAmong 738 cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA–IV treated at our institution, 96 (13%) presented with CA histology. The blood samples, collected within 10 days before treatment, were analyzed using a Sysmex XN-2000 system. The statistical tests included Mann–Whitney U-tests, log-rank tests, and Cox regression models. The cutoff points for the calculated hematological coefficients (NLR, PLR, and MLR) were determined using the MedCalc statistical program.ResultsThe prognostic factor for overall survival (OS) and recurrence-free survival (RFS) in CA was clinical stage according to FIGO classification (FIGO IIB–IV vs I–IIA) (P=0.0001; P=0.002). Among patients with FIGO stage IIB–IV treated with radiotherapy/chemoradiotherapy, an elevated PLR was a negative prognostic factor for OS (P=0.017; HR: 2.96; 95% CI: 2.069–3.853). Among all patients, an elevated pretreatment NLR was a poor prognostic factor for OS (P=0.014; HR: 2.85; 95% CI: 2.011–3.685) and RFS (P=0.049; HR: 4.0; 95% CI: 2.612–5.392). The white blood cell count (WBC) before treatment was significantly higher in patients who died during follow-up (P=0.009).ConclusionElevated NLR values before treatment may be associated with a shorter time of RFS and OS, while PLR index may have prognostic significance for OS in patients with advanced disease (FIGO IIB–IV). Both indexes and WBC may be a cost-effective biomarker that can be used conveniently for stratification of recurrence risk and death.

The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I–III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7 %; 35 patients died; and the 3-year overall survival (OS) rate was 85 %. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61 % (p = 0.014) and overall survival −88 vs. 82 % (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59 % of patients with ulceration and in 26 % of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I–III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.

IL-1ra and IL-8 concentrations in serum, together with a lack of estrogen and progesterone receptors in tumor cells, in breast cancer patients older than 50 years could represent additional predictive factors for this disease.

The aim of the study was to evaluate the utility of the measurements of the circulating tumor markers, squamous cell carcinoma antigen (SCCA), CA125, carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21.1), and the cytokines, interleukin-6 and vascular endothelial growth factor (VEGF), to estimate regional lymph node involvement in patients with cervical cancer. The study comprised 182 untreated patients with cervical cancer. The regional lymph node status was assessed either by the postsurgical histopathologic examination or by the computed tomography (CT). Concentrations of SCCA, CEA, and CA125 were determined using the Abbott Instruments system, of CYFRA 21.1 by the Roche kits, and of IL-6 and VEGF by the ELISA of R&D Systems (Minneapolis, MN). For the statistical analyses, Mann-Whitney U test and chi(2) test were applied. Serum levels of SCCA, CEA, CA125, CYFRA 21.1, IL-6, and VEGF were measured in patients with specified pelvic and para-aortic lymph node status. SCCA, CA125, and IL-6 levels were found to be significantly higher in patients with lymph node metastases than in those with no lymph node involvement. Also, the percentage of patients with simultaneously elevated concentrations of SCCA and CA125 or SCCA and IL-6 differed depending on the lymph node status and was significantly higher in the series of patients with lymph node metastases. Simultaneous assessment of serum levels of SCCA and CA125 or SCCA and IL-6 in patients with cervical cancer may be useful for the regional lymph node evaluation, especially in patients with advanced stages, when the lymph nodes are examined only by CT, with no histologic confirmation.

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