Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

A cancer associated fibroblasts (CAFs) specific gene signature in high grade serous ovarian cancer

ABSTRACT: Ovarian cancer is the most lethal malignancy in the United States. In the year 2012, there will be an estimated 22,280 new cases and 15,500 deaths from ovarian cancer in the country (Siegel et al., 2012). While studies on ovarian cancer pathogenesis were mainly focused on the epithelial component of the tumor, understanding in the role of cancer associated fibroblasts (CAFs) in ovarian cancer progression is limited. We hypothesized that comparing the gene expression profiles of different components from laser capture microdissected ovarian tissue will allow us to identify an ovarian CAFs specific gene signature which accounts for the supportive role of CAFs in ovarian cancer progression. In this study, gene expression profiling was completed for 31 cancer stroma samples and 32 samples of epithelial component from high grade serous ovarian cancer patients. 8 microdissected normal ovarian stroma and 6 normal human ovarian surface epithelium (HOSE) samples were also included in the study. By comparing the expression data from cancer stroma against that from normal stroma, cancer cells and HOSE, we identified a set of differential expressed genes in ovarian CAFs which showed correlation with cancer patient survival. Further study on these genes can reveal their roles in ovarian cancer progression and pathogenesis. Ultimately, ovarian CAFs specified genes identified in this study may aid in the classification and enhancement of patient outcome. Transcriptome profiling analyses were performed on 31 laser microdissected cancer associated stroma samples, 32 epithelial tumor samples from high grade serous ovarian cancer patients, 8 microdissected normal ovarian stroma samples and 6 ovarian surface epthelium (HOSE) samples using the Affymetrix human genome U133 Plus 2.0 microarray.

ORGANISM(S): Homo sapiens

SUBMITTER: Tsz-Lun Yeung

PROVIDER: E-GEOD-40595 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.

Yeung Tsz-Lun TL Leung Cecilia S CS Wong Kwong-Kwok KK Samimi Goli G Thompson Melissa S MS Liu Jinsong J Zaid Tarrik M TM Ghosh Sue S Birrer Michael J MJ Mok Samuel C SC

Cancer research 20130703 16

TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts (CAF) that are present in the microenvironment. Transcriptome profiling of microdissected stromal and epithelial components of high-grade serous ovarian tumors and TGF-β-treated no ...[more]

PMID: 23824740

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Project description:Low-grade serous ovarian carcinoma is believed to arise from serous borderline ovarian tumors, yet the progression from serous borderline tumors to low-grade serous ovarian carcinoma remains poorly understood. The purpose of this study was to identify differentially expressed genes between the two groups. Expression profiles were generated from 6 human ovarian surface epithelia (HOSE), 8 serous borderline ovarian tumors (SBOT), 13 low-grade serous ovarian carcinomas (LG), and 22 high-grade serous ovarian carcinomas (HG). The anterior gradient homolog 3 (AGR3) gene was found to be highly upregulated in serous borderline ovarian tumors; this finding was validated by real-time quantitative RT-PCR, Western blotting, and immunohistochemistry. Anti-AGR3 immunohistochemistry was performed on an additional 56 LG and 103 HG tissues and the results were correlated with clinical data. Expression profiling determined that 1254 genes were differentially expressed (P < 0.005) between SBOT, LG and HG tumors. Serous borderline ovarian tumors exhibited robust positive staining for AGR3, with a lower percentage of tumor cells stained in LG and HG. Immunofluorescence staining indicated that AGR3 expression was limited to ciliated cells. Tumor samples with a high percentage (>10%) of AGR3 positively stained tumor cells were associated with improved longer median survival in both the LG (P = 0.013) and HG (P = 0.008) serous ovarian carcinoma groups. The progression of serous borderline ovarian tumors to low-grade serous ovarian carcinoma may involve the de-differentiation of ciliated cells. AGR3 could serve as a prognostic marker for survival in patients with low-grade and high-grade serous ovarian carcinomas. Total RNA were extracted from microdissected human ovarian surface epithelia (HOSE, n=6), and microdissected serous borderline ovarian tumors (LMP, n=8), low-grade serous ovarian carcinomas (LGOSC, n=13), and 22 high-grade serous ovarian carcinomas (HGOSC, n=22). Gene Expression profiles were then generated with commercial GeneChip Human Genome U133 Plus 2.0 Array. dChip was used to identify significant differentially expressed genes between LMP/LGOSC and HGOSC

Project description:Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis. The purpose of this study was to identify candidate genes possibly involved in pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected in comparison with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples, and also high grade serous carcinoma samples collected from patients with BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when statistically compared to controls pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes were upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies. Both fallopian tube and ovarian samples were collected from each BRCA1/2 mutation carrier resulting in eighteen mutation positive adnexal samples. Both fallopian tube and ovarian control samples were collected from one control patient while either ovarian or fallopian tube sample was available from four control patients, respectively, resulting in 6 adnexal control samples. High quality RNA was available from nine BRCA1/2-mutation positive ovarian and eight BRCA1/2-mutation positive fallopian tube samples and from three control ovarian and three control fallopian tube samples.

Dataset Information

A cancer associated fibroblasts (CAFs) specific gene signature in high grade serous ovarian cancer

Publications

TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment.

Similar Datasets

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