BackgroundIn ammation is a hallmark of cancer, and emerging light is being shed on the neutrophil release of nuclear chromatin, referred to as neutrophil extracellular traps (NETs) in cancer and cancer associated thrombosis. The NET-speci c marker citrullinated histone H3 (H3Cit) has been found to be elevated in plasma from patients with malignancies, suggesting the potential of NET markers, such as H3Cit, as novel cancer biomarkers. ObjectiveTo determine the levels of plasma H3Cit in blood in women with adnexal masses. Subjects and Methods: Peripheral blood samples were obtained preoperatively from 199 patients admitted for primary surgery of adnexal masses 2015-2017. Patients were grouped according to tumor type and stage of cancer. Plasma levels of H3Cit-DNA, cell free DNA (cfDNA) and the clinically implemented tumor marker cancer antigen 125 (CA125) were determined with ELISA. ResultsPlasma levels of H3Cit-DNA and cfDNA were not elevated in women with borderline or malignant ovarian tumors compared with women with benign tumors. Increased plasma levels of CA125 were detected in borderline and ovarian cancer stage I and stage II-IV compared with benign ovarian tumor patients (p trend <0.001). In Cox regression analysis high levels of Ca 125 dichotomized at 326 IU/ml (median) showed worse overall survival hazard ratio 1.9 (95 % C.I. 1.03-3.36; p = 0.038). No differences were found in the survival analyses in malignant ovarian tumors analyzing the cfDNA and H3Cit-DNA levels. ConclusionThis study did not nd any association nor prognostic association between the plasma levels of the NET marker H3Cit and ovarian cancer patients.
Background/Aim: Epithelial ovarian cancer (EOC) is usually diagnosed in advanced stages and has a high mortality rate. In this study, we used the proximity extension assay from Olink Proteomics to search for new plasma protein biomarkers to predict overall survival (OS) in patients with EOC. Materials and Methods: Peripheral blood samples were obtained preoperatively from 116 EOC patients undergoing primary debulking surgery: 28 early EOC cases (FIGO stage I-II) and 88 advanced EOC cases (FIGO stage III-IV). Proteins were measured using the Olink Oncology II and Inflammation panels. In total, 177 unique protein biomarkers were analysed. Cross-validation and LASSO regression were combined to select prediction models for OS. Results: The model including age and the three-biomarker combination of neurotrophin-3 (NT-3)+transmembrane glycoprotein NMB (GPNMB)+mesothelin (MSLN) predicted worse OS with AUC=0.79 (p=0.004). Adding cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) to the model further improved performance (AUC=0.83; p=0.003). In a postoperative model including age and stage (III+IV vs. I+II), the three-biomarker panel of chemokine (C-C motif) ligand 28 (CCL28)+T-cell leukaemia/lymphoma protein 1A (TCL1A)+GPNMB improved the prediction of OS (from AUC=0.83 to AUC=0.90; p=0.05). In the postoperative model including age and dichotomized stage (III vs. I+II), the biomarkers CCL28 and GPNMB1 improved the prediction of OS (AUC=0.86; p<0.001). The combination of high levels of both CA125 and HE4 predicted worse survival (p=0.05). Conclusion: In this explorative study evaluating the performance of plasma protein biomarkers in predicting OS, we found that adding biomarkers, especially NT-3, to the panel improved the prediction of OS.
were studied for mRNA levels of TGF-b1 ligand, TGF-b receptor1 & 2 (TGFbRI&II), Smad2 and Smad4 genes. mRNA expression was quantified by delta Ct (DCt) values obtained from quantitative PCR tests and fold change in expression by DDCt values from DCt of reference endometrial sample. The association of these mRNA expressions with tumour-related characteristics and recurrences was assessed using non-parametric tests as Mann-Whitney U test & Kruskal Wallis test. Results 49 patients were considered for analysis. Majority were of endometrioid histology, lower grade, and stage I. 84% of endometrial cancer samples demonstrated underexpression of Smad2. Loss of Smad2 was significantly associated with myo-invasive tumours and tumours >2 cm. Loss of TGFbRII expression was related to parametrial invasion and stage IV disease, while reduced TGFbRI expression to clear cell histology. During a median follow up of 15.4 months, there were three recurrences. Loss of TGFbRII expressions was significantly associated with recurrence. Mean DDCt value of >1.950 for smad2 and TGFbRII expression was associated significantly with a reduced 1.5 year recurrence-free survival. Conclusion TGFb pathway components undergo changes in endometrial cancer. Impaired expression is observed at every level of signalling pathway, Loss of Smad mRNA expression and TGFb receptor levels have certain associations with aggressive features and can predict recurrence risk.
Background Circulating tumor DNA (ctDNA), which is shed from tumor cells into the blood, is a promising minimal-invasive method for cancer diagnostics and monitoring. The aim of this study was to evaluate preoperative ctDNA levels in the plasma of patients with ovarian cancer and correlate the levels to clinicopathological parameters and patient outcome. Methods Tumor DNA was extracted from ovarian tumor tissue from 41 patients. Targeted sequencing using a panel of 127 genes recurrently mutated in cancer was performed to identify candidate somatic mutations in the tumor DNA. SAGAsafe digital PCR (dPCR) assays targeting the candidate mutations were used to measure ctDNA levels in patient plasma samples, obtained prior to surgery, to evaluate ctDNA levels in terms of mutant copy number/mL and variant allele frequency. Results Somatic mutations were found in 24 tumors, of which seven were from patients with borderline, and 17 with invasive cancer diagnosis. TP53 was the most frequently mutated gene. Fifteen of 24 patients had detectable ctDNA levels in pre-operative plasma. Plasma ctDNA mutant concentration increased with higher stage (ptrend <0.001). Cancer patients with more than 10 ctDNA mutant copies/mL in plasma prior to surgery had significantly worse overall survival (p = 0.008). Conclusions Measuring ctDNA in pre-operative plasma may be useful as a predictive biomarker for tumor staging and prognosis in ovarian cancer patients.
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