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.
Project description:Ovarian cancer is the most lethal gynecologic cancer. High-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype, accounting for three quarters of ovarian cancer. To clarify the changes of gene expression in serous ovarian cancer, we performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in High-grade and Low-grade serous ovarian carcinoma compared with Normal fallopian tube.
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.
Project description:Fallopian tube epithelium is the tissue-of-origin of most high grade serous papillary ovarian carcinoma. This tumor has been exensively investigated and sequenced but expression profiling data of normal fallopian tube epithelial cells is still rare. This project compares the miRNA profiles of high grade serous papillary ovarian tumors (FFPE and fresh frozen) to that of normal unmatched epithelial cells from resected fallopian tubes.
Project description:Comparative genomic hybridization analysis on advanced stage high-grade serous ovarian cancer. CGH was performed on 42 DNA isolated from microdissected advanced stage high-grade serous ovarian cancer.
Project description:Background: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. Methods: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with the same standard platinum-based chemotherapy. Twelve patient tumors demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumors from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using a Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumors from the resistant group and the sensitive group. Results: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels, which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NFκB/ERK gene signalling networks. Conclusions: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. Future studies to validate these markers are necessary to apply this knowledge to biomarker-based clinical trials. Total RNA from 12 chemotherapy resistant and 16 sensitive chemotherapy sensitive high-grade serous epithelial ovarian cancer samples was subjected to whole transcriptome profiling using Affymetrix U133 Plus 2.0 arrays