Dataset Information

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

ABSTRACT: The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes.Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n=56) was done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data.Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression-free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential.VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression-free survival and platinum resistance.

SUBMITTER: Ghosh S

PROVIDER: S-EPMC3000175 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

Ghosh Sue S Albitar Lina L LeBaron Richard R Welch William R WR Samimi Goli G Birrer Michael J MJ Berkowitz Ross S RS Mok Samuel C SC

Gynecologic oncology 20100708 1

<h4>Objective</h4>The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes.<h4>Methods</h4>Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and q ...[more]

PMID: 20619446

Similar Datasets

Project description:To identify and evaluate the prognostic ability of progression-free survival-related profile for advanced-stage ovarian cancer, advanced-stage serous ovarian cancer tissues from 110 patients who received primary surgery and a platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays of more than 40,000 transcripts. We first selected 88 genes by a univariate Cox proportional hazard analysis (p<0.01) and next optimized regression coefficients by ridge regression model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p,0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). In multivariable analysis, our prognostic index was independently associated with progression-free survival times compared to other clinical factors (p<0.001). Furthermore, the prognostic ability of our prognostic index was validated in external, publicly available dataset (n = 87), and was proved in multivariate analysis (p = 0.0032). These results suggest that disease progression or recurrence of advanced-stage serous ovarian cancer can be predicted by gene expression profile. The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.

Dataset Information

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

Publications

Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets