Diagnostic performance of the biomarkers HE4 and CA125 in type I and type II epithelial ovarian cancer

AbstractObjectiveTo evaluate the diagnostic performance of HE4 and CA125 in patients presenting with suspicious malignant ovarian cysts. We especially wanted to investigate the levels of HE4 and CA125 with regard to the gene and histology-unifying model of type I and type II epithelial ovarian cancer (EOC).MethodsPlasma from 373 women presenting with a suspicious malignant ovarian cyst was collected prior to surgery. Histology, grade, and stage were determined according to FIGO-classification. HE4 and CA125 were analyzed using ELISA, and the markers were evaluated for significance separately and in combination. Receiver operating curves, the area under the curve, sensitivity and specificity were estimated.ResultsThe combination of HE4 and CA125 resulted in the best diagnostic power in comparing benign tumors to EOC (ROC AUC 0.93, sensitivity 94.4% at 75% specificity) for type II. Diagnostic power in type I (ROC AUC 0.79, sensitivity 61.9% at 75% specificity) was less impressive. In particular, mucinous benign vs. malignant tumors could not significantly be separated by the dual marker combination. Impressively high ROC AUC 0.99 was found for the late stage type II EOC with 100% sensitivity at 75% specificity.ConclusionsHE4 and CA125 have a good ability to diagnose the more aggressive type II tumors but a poor diagnostic ability when patients are presenting with slow-growing type I in the early stage. Our results support the hypothesis that EOC should be looked upon as several different diseases, and that we lack biomarkers for sub-groups of EOC

Saturated Fat Intake Is Associated with Lung Function in Individuals with Airflow Obstruction: Results from NHANES 2007⁻2012

Nutritional status is a well-recognized prognostic indicator in chronic obstructive pulmonary disease (COPD); however, very little is known about the relationship between lung function and saturated fat intake. We used data from the cross-sectional National Health and Nutrition Examination Surveys (NHANES) to assess the relationship between saturated fatty acid (SFA) intake and lung function in the general US adult population. Adults in NHANES (2007⁻2012) with pre-bronchodilator spirometry measurements and dietary SFA intake were included. Primary outcomes were lung function including forced expiratory volume in one second (FEV₁

External validation suggests Integrin beta 3 as prognostic biomarker in serous ovarian adenocarcinomas

<p>Abstract</p> <p>Background</p> <p>The majority of women with ovarian cancer are diagnosed in late stages, and the mortality rate is high. The use of biomarkers as prognostic factors may improve the treatment and clinical outcome of these patients. We performed an external validation of the potential biomarkers CLU, ITGB3, CAPG, and PRAME to determine if the expression levels are relevant to use as prognostic factors.</p> <p>Methods</p> <p>We analysed the gene expression of CLU, ITGB3, CAPG, and PRAME in 30 advanced staged serous adenocarcinomas with quantitative real-time polymerase chain reaction (QPCR) and the protein levels were analysed in 98 serous adenocarcinomas with western blot for semiquantitative analysis. Statistical differences in mRNA and protein expressions between tumours from survivors and tumours from deceased patients were evaluated using the Mann-Whitney U test.</p> <p>Results</p> <p>The gene and protein ITGB3 (Integrin beta 3) were significantly more expressed in tumours from survivors compared to tumours from deceased patients, which is in concordance with our previous results. However, no significant differences were detected for the other three genes or proteins CLU, CAPG, and PRAME.</p> <p>Conclusion</p> <p>The loss of ITGB3 expression in tumours from deceased patients and high expression in tumours from survivors could be used as a biomarker for patients with advanced serous tumours.</p

Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

<p>Abstract</p> <p>Background</p> <p>Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers.</p> <p>Methods</p> <p>To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (<it>EVI1</it>, <it>MDS1</it>, <it>SH3GL2</it>, <it>SH3KBP1</it>) plus the <it>ABCB1 </it>gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level.</p> <p>Results</p> <p>We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, <it>EVI1 </it>expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group.</p> <p>Conclusion</p> <p>In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Skaitmeninių vartotojų tipai Lietuvoje ir Gruzijoje: ypatumai pardavimo skatinimo kontekste

The paper presents the determination of types of digital consumers in Lithuania and Georgia and their response to the techniques of online sales promotion. Firstly, readers are introduced with the theoretical classification of digital consumers and online sales promotion techniques. Then, the methodological principles of the research identifying Lithuanian and Georgian types of digital consumer and their response to the techniques of the online sales promotion are defined. The results of the research are presented; the comparative analysis of both countries based on the main findings are introduced

Digital consumer types in Lithuania and Georgia: peculiarities in the context of sales promotion

Ekonomikos ir vadybos fakultetasMarketingo katedraVytauto Didžiojo universiteta