Transcription profiling of human late-stage, high-grade papillary serous ovarian adenocarcinomas
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Michael Birrer
PROVIDER: E-GEOD-18520 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series:; GSE18373: Expression data of HUVEC and OVCA429 with recombinant MAGP2; GSE18520: Whole-genome oligonucleotide expression analysis of papillary serous ovarian adenocarcinomas Experiment Overall Design: Refer to individual Series
2009-10-23 | E-GEOD-18521 | biostudies-arrayexpress
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
2011-03-04 | E-GEOD-27651 | biostudies-arrayexpress
Project description:To demonstrate the use of a whole-genome oligonucleotide array to perform expression profiling on a series of microdissected late-stage, high-grade papillary serous ovarian adenocarcinomas to establish a prognostic gene signature correlating with survival and to identify novel survival factors in ovarian cancer. Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. We identify and validate a prognostic gene expression signature correlating with survival in a series of microdissected serous ovarian tumors.
2009-10-17 | GSE18520 | GEO
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.
2011-03-04 | GSE27651 | GEO
Project description:To elucidate the mechanisms of rapid progression of serous ovarian cancer, gene expression profiles from forty-three ovarian cancer tissues comprising eight early stage and thirty-five advanced stage tissues were performed using oligonucleotide microarrays of 18,716 genes. By non-negative matrix factorization analysis using 178 genes, which were extracted as stage-specific genes, 35 advanced-stage cases were classified into two subclasses with superior (n = 17) and poor (n = 18) outcome evaluated by progression-free survival (logrank test, p = 0.03). Of the 178 stage-specific genes, 112 genes were identified as showing different expression between the two subclasses. Of the 48 genes selected for biological function by Gene Ontology analysis or Ingenuity Pathway Analysis, 5 genes (ZEB2, CDH1, LTBP2, COL16A1 and ACTA2) were extracted as candidates for prognostic factors associated with progression-free survival. The relationship between high ZEB2 or low CDH1 expression and shorter progression-free survival was validated by real-time RT-PCR experiments of 37 independent advanced-stage cancer samples. ZEB2 expression was negatively correlated with CDH1 expression in advanced-stage samples, whereas ZEB2 knockdown in ovarian adenocarcinoma SKOV3 cells resulted in an increase in CDH1 expression. Multivariate analysis showed that high ZEB2 expression was independently associated with poor prognosis. Furthermore, the prognostic effect of E-cadherin encoded by CDH1 was verified using immunohistochemical analysis of an independent advanced-stage cancer samples set (n = 74). These findings suggest that the expressions of epithelial-mesenchymal transition-related genes such as ZEB2 and CDH1 may play important roles in the invasion process of advanced-stage serous ovarian cancer. Forty-three serous ovarian cancer samples were analyzed. Ten normal peritoneum samples were used as controls.
2009-07-19 | E-GEOD-12470 | biostudies-arrayexpress
Project description:Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Low-grade ovarian serous carcinomas are believed to arise via an adenoma-serous borderline tumor-serous carcinoma sequence. In this study, we found that advanced-stage, low-grade ovarian serous carcinomas both with and without adjacent serous borderline tumor shared similar regions of loss of heterozygosity. We then analyzed 91 ovarian tumor samples for mutations in TP53, BRAF, and KRAS. TP53 mutations were not detected in any serous borderline tumors (n = 30) or low-grade serous carcinomas (n = 43) but were found in 73% of high-grade serous carcinomas (n = 18). BRAF (n = 9) or KRAS (n = 5) mutation was detected in 47% of serous borderline tumors, but among the low-grade serous carcinomas (39 stage III, 2 stage II, and 2 stage I), only one (2%) had a BRAF mutation and eight (19%) had a KRAS mutation. The low frequency of BRAF mutations in advanced-stage, low-grade serous carcinomas, which contrasts with previous findings, suggests that aggressive, low-grade serous carcinomas are more likely derived from serous borderline tumors without BRAF mutation. In addition, advanced-stage, low-grade carcinoma patients with BRAF or KRAS mutation have a better apparent clinical outcome. However, further investigation is needed. Gene expression analysis was performed on five serous borderline tumors with BRAF mutation and five serous borderline tumors without BRAF mutation randomly. RNA was extracted from microdissected tumor cells. Expression profiling was carried out with Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays
2011-03-04 | E-GEOD-27659 | biostudies-arrayexpress
Project description:The Japanese Serous Ovarian Cancer Study Group Advanced-stage ovarian cancer is one of the most lethal gynecologic malignancies. To improve prognosis of patients with ovarian cancers, a predictive biomarkers leading to personalized treatments are required. In this large-scale cross-platform study of six microarray datasets consisting of 1054 ovarian cancer patients, we developed a novel risk classification system based on a 126-gene expression signature for predicting overall survival by applying elastic net7 and 10-fold cross validation to a Japanese dataset A (n = 260). We further validated its predictive ability with the five other datasets using multivariate analysis. Also, through gene ontology and pathway analyses of 1109 high-risk ovarian cancer specific transcripts, we identified a significant reduction of expression of immune-response related genes, especially on the antigen presentation pathway. Furthermore, an immunohistochemical analysis demonstrated that the number of CD8 T lymphocytes infiltrating into tumor tissue was significantly decreased in high-risk ovarian cancers. These predictive biomarkers based on the 126-gene expression signature will identify high-risk ovarian cancer patients who need novel immune-activating therapeutic approaches, leading to improved outcomes for such patients. Two hundred sixty patients who were diagnosed as advanced-stage high-grade serous ovarian cancer were analyzed in this study. Microaray data from 10 patients who were diagnosed as advanced-stage high-grade serous ovarian cancer were analyzed to investigate coefficient of correlation in each probes between Agilent Whole Human Genome Oligo Microarray and Affymetrix HG-U133Plus2.0.
2012-03-01 | E-GEOD-32062 | biostudies-arrayexpress
Project description:PAX2 is one of nine PAX genes that regulate tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell lineage specification, migration, and survival. In our previous study, we found that PAX2 is highly expressed in low-grade ovarian serous carcinoma, but its expression in clear cell, endometrioid, and mucinous cell ovarian carcinomas have not been studied. More importantly, the functional role of PAX2 in ovarian cancer is not known. Downregulation of PAX2 in PAX2-expressing ovarian cancer cells inhibits cell proliferation and migration. This growth inhibition is due to the upregulation of the tumor suppressor gene G0S2 and subsequent induction of apoptosis. The PAX2 pathway thus represents a potential therapeutic target for PAX2-expressing ovarian carcinomas. Knockdown PAX2 expression in these cell lines was achieved by lentiviral shRNAs targeting the PAX2 gene. PAX2 stable knockdown cells were characterized for cell proliferation, migration, apoptosis, and gene expression profiles.
2011-12-05 | E-GEOD-30501 | biostudies-arrayexpress
Project description:The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art Taqman-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment (complete response - CR vs. other), and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS: log-rank p=0.0000 and PFS: log-rank p=0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions. In the study presented here, effusion samples were obtained from 32 patients diagnosed with serous ovarian carcinoma (n=25), primary peritoneal serous carcinoma (n=6) or tubal serous carcinoma (n=1). They were accrued at the Division of Pathology in the Norwegian Radium Hospital from 2000-2006. RNA was used to study the expression profile of 381 multidrug resistant-related genes.
2011-11-17 | E-GEOD-29702 | biostudies-arrayexpress
Project description:To date, a variety of studies have employed gene expression profiling to classify ovarian carcinomas in clinically relevant subtypes. These studies provided valuable first clues to molecular changes in ovarian cancer that might be exploited in new treatment strategies. However, most studies were of relatively limited size and the number of overlapping genes in the identified profiles was minimal. Although identification of gene expression profiles associated with clinically relevant subtypes in ovarian cancer is important, knowledge is now emerging rapidly on how genes interact in pathways, networks and complexes; this allows us to unravel those cellular pathways determining the biological behavior of ovarian cancer, that might be successfully targeted with drugs. The aim of our study was: 1) To develop a gene expression profile associated with overall survival in advanced stage serous ovarian cancer, 2) to assess the association of pathways and transcription factors with overall survival, and 3) to validate our identified profile and pathways/transcription factors in an independent set of ovarian cancers. According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using ~35K 70-mer oligonucleotide microarrays. A continuous predictor of overall survival was built taking into account well-known issues in microarray analysis, such as multiple testing and overfitting. A functional class scoring analysis was utilized to assess pathways/transcription factors for their association with overall survival. The prognostic value of genes that constitute our overall survival profile was validated on a fully independent, publicly available data set of 118 well-defined primary serous ovarian cancers. Furthermore, functional class scoring analysis was also performed on this independent data set to assess the similarities with results from our own data set. An 86-gene overall survival profile discriminated between patients with unfavorable and favorable prognosis (median survival, 19 vs. 41 months, respectively; permutation p-value of log-rank statistic = 0.015) and maintained its independent prognostic value in multivariate analysis. Genes that comprised the overall survival profile were also able to discriminate between the two risk groups in the independent data set. In our dataset 17/167 pathways and 13/111 transcription factors were associated with overall survival of which 16 and 12 respectively were confirmed in the independent dataset. Our study provides new clues to genes, pathways and transcription factors which contribute to the clinical outcome of serous ovarian cancer and might be exploited in designing new treatment strategies. Keywords: Oncology/Gynecological Cancers, Genetics and Genomics/Cancer Genetics, Genetics and Genomics/Gene Expression, Genetics and Genomics/Genomics According to a randomized design, profiling of 157 advanced stage serous ovarian cancers was performed in duplicate using ~35K 70-mer oligonucleotide microarrays. Two randomly selected samples were hybridized together on the arrays for intensity-based instead of ratio-based analysis of the microarray data.
2008-12-10 | E-GEOD-13876 | biostudies-arrayexpress