In plasma samples obtained during menstruation, multivariate analysis of four biomarkers (annexin V, VEGF, CA-125 and sICAM-1/or glycodelin) enabled the diagnosis of endometriosis undetectable by US with a sensitivity of 81-90% and a specificity of 63-81% in independent training- and test data set. The next step is to apply these models for preoperative prediction of endometriosis in an independent set of patients with infertility and/or pain without US evidence of endometriosis, scheduled for laparoscopy.

Massively parallel sequencing greatly facilitates the discovery of novel disease genes causing Mendelian and oligogenic disorders. However, many mutations are present in any individual genome, and identifying which ones are disease causing remains a largely open problem. We introduce eXtasy, an approach to prioritize nonsynonymous single-nucleotide variants (nSNVs) that substantially improves prediction of disease-causing variants in exome sequencing data by integrating variant impact prediction, haploinsufficiency prediction and phenotype-specific gene prioritization.

The Serbian version of CLDQ is well accepted and represents a valid and reliable instrument in Serbian sample of CLD patients.

Purpose: Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.Experimental Design: Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray datasets. These datasets were further used to downsize and optimize a gene score, which was subsequently determined in paraffin-embedded material of 126 patients with colon cancer treated in our center.Results: In the CaCo-2 cells, 923 genes with a 2-fold change and Limma corrected P 0.0001 were found differentially expressed in hypoxia versus normoxia. We identified 21 genes with prognostic value and overlapping in three different training sets and (n ¼ 224). With a fourth published dataset (n ¼ 177), the sixgene Colon Cancer Hypoxia Score (CCHS) was developed. Patients with low CCHS showed a significant better disease-free survival at three years (77.3%) compared with high CCHS patients (46.4%; log-rank, P ¼ 0.006). This was independently confirmed in an external patient cohort of 90 stage II patients (86.9% vs. 52.2%; P ¼ 0.001).Conclusions: Hypoxia-driven gene expression is associated with high recurrence rates in stage II and III colon cancer. A six-gene score was found to be of independent prognostic value in these patients. Our findings require further validation and incorporation in the current knowledge on molecular classification of colon cancer. Clin Cancer Res; 20(8); 2159-68. Ó2014 AACR.