Publications by authors named "Izabela Baryła"

Background: Although the WW-domain-containing oxidoreductase (WWOX)/Hypoxia-inducible factor 1 (HIF1) pathway is a well-known regulator of cellular glucose and energy metabolism in pathophysiological processes, its role in gestational diabetes mellitus (GDM), remains elusive. We undertook this study to determine the effect of WWOX/HIF1A signaling on the expression of glucose metabolism genes in GDM patients.

Methods: Leukocytes were obtained from 135 pregnant women with ( = 98) or without ( = 37) GDM and, in turn, 3 months ( = 8) and 1 year ( = 12) postpartum. Quantitative RT-PCR was performed to determine gene expression profiles of the WWOX/HIF1A-related genes, including those involved in glucose transport (), glycolytic pathway (), Wnt pathway (), and inflammatory response ().

Results: GDM patients displayed a significant downregulation of with simultaneous upregulation of which resulted in approximately six times reduction in ratio. As a consequence, induced genes () were found to be overexpressed in GDM compared to normal pregnancy and negative correlate with ratio. The postpartum expression was higher than during GDM, but its level was comparable to that observed in normal pregnancy.

Conclusions: The obtained results suggest a significant contribution of the gene to glucose metabolism in patients with gestational diabetes. Decreased expression in GDM compared to normal pregnancy, and in particular reduction of ratio, indicate that WWOX modulates HIF1α activity in normal tissues as described in the tumor. The effect of HIF1α excessive activation is to increase the expression of genes encoding proteins directly involved in the glycolysis which may lead to pathological changes in glucose metabolism observed in gestational diabetes.

Uterine corpus endometrial carcinomas (UCEC) are clinically divided into two subgroups-endometrioid endometrial carcinoma (EEC) or non-endometrioid endometrial carcinoma (NEEC). The first group shows relatively better prognosis. However, the discrimination seems to be insufficient due to the fact that in the mildest EEC are patients with poor treatment response and bad prognosis. Our aim was to examine the molecular background of such phenomenon and whether gene expression patterns might be of importance for the clinic. We focused our analysis on WNT pathway target genes since it is one of the main regulators of endometrial proliferation and differentiation. analysis of TCGA data, including Weighted Co-expression Network Analysis, Principle Component Analysis, and Multiple Factor Analysis, allows to select 28 genes that serve as a predictive markers for UCEC patients. Our study revealed that there is a subgroup of the endometrioid cases that molecularly resembles mixed/serous groups. This may explain the reason for existence of subgroup of patients, that although clinically diagnosed with the mildest endometrioid UCEC type, yet present failure in treatment and aggressive course of the disease. Our study suggests that worse outcome in these patients may be based on a disruption of proper WNT signalling pathway resulting in deregulation of its effector genes. Moreover, we showed that mixed group consisting of tumours containing both endometrioid and serous types of cells, has serous expression profile of WNT targets. The proposed gene set allows to predict progression of the disease trough dividing patients into groups of low or high grade with 70.8% sensitivity and 88.6% specificity (AUC = 0.837) as well as could predict patient prognosis associated with UCEC subtype with 70.1% sensitivity and 86.2% specificity (AUC = 0.855). Relatively small number of implicated genes makes it highly applicable and possibly clinically simple and useful tool.

WWOX gene is located in FRA16D, the highly affected chromosomal fragile site. Its tumor suppressor activity has been proposed on a basis of numerous genomic alterations reported in chromosome 16q23.3-24.1 locus. WWOX is affected in many cancers, showing as high as 80% loss of heterozygosity in breast tumors. Unlike most tumor suppressors impairing of both alleles of WWOX is very rare. Despite cellular and animal models information on a WWOX role in cancer tissue is limited and sometimes confusing. This review summarizes information on WWOX in human tumors.