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Identification of differentially expressed transcription factors in ovarian cancer

ABSTRACT: Ovarian cancer is the fifth most common form of cancer in women in the United States. Epithelial ovarian cancer is the most common and is highly lethal. In 2014, there will be an estimated 21,980 new cases and 14,270 deaths from ovarian cancer in the United States. No major strides have been made to improve survival over the past decade. Ovarian cancer is notable for initial chemotherapy sensitivity (>75% response rates) using combination platinum and taxane chemotherapy following debulking surgery. However, eventually, the vast majority of these women (>75-80%) will have their cancer recur within 12 to 24 months after diagnosis and will die of progressively chemotherapy-resistant diseases. Transcription factors act as master switches of various biochemical pathways by regulating gene transcription. Large number of studies demonstrated the role of transcription factors in cancer development and progression. However, transcription factors involved in the pathogenesis of ovarian cancer have not been explored thoroughly. Therefore, we propose to using transcriptome profiling to generate a transcription factor gene signature for high-grade serous ovarian cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE54388 | GEO | 2017/06/05

SECONDARY ACCESSION(S): PRJNA236379

REPOSITORIES: GEO

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Project description:Tumor specimens were collected from women with ovarian tumors at primary surgery in a study covering most of Denmark called the MALOVA-study (MALignant OVArian cancer study). This multidisciplinary study on ovarian cancer covers epidemiology (life style factors), biochemistry, and molecular biology with the purpose of identifying risk factors and prognostic factors for EOC. The study has been approved by the Scientific Ethic Committees in the study area (KF01-384/95). Sample collection went on from 1994 to 1999, and the study is described in details in other articles(20;21;24;30). Histopathological classification of the ovarian tumors was based on the typing criteria of the WHO. Pathology reports and tissue were collected from the participating hospitals. One pathologist specialized in ovarian tumors, reviewed the tissue specimens without knowledge of the primary diagnoses. Subsequently, the reviewed diagnosis was compared to the original diagnosis and agreement on invasiveness was present in 98 % of the cases. The histopathological type was refined in 14% of the cases. FIGO stages were obtained from clinical records and were reviewed by two gynecologists, both specialized in OC. Reviewed data were used for further analysis. Furthermore all other relevant hospital files were collected, and data concerning, debulking status, CA-125 level prior to operation, amount and type of chemotherapy and cause of death (if dead) were registered. Patients were scored as ÂradicalÂ (optimally debulked) if no macroscopic residual tumor nodules were left, and as Ânon-radicalÂ (sub-optimally debulked) if macroscopic nodules were left. All fresh tumor samples included in this study were intended to be snap frozen within 20 minutes after the tumor was removed, but exact transportation time is not known. All samples have been stored at -80ÂºC. We selected samples from the largest and most common histological subtype, the serous ovarian cancers, all stages. The tumor sample material consisted of 70 stage III/IV tumors and 19 stage I/II tumors. Further patient information can be obtained from the submitters on request.

Project description:Advanced ovarian cancer is the most lethal gynecologic malignancy in the United States. Currently patients are treated by surgical cytoreductive surgery with the aim of reducing tumor burden to microscopic disease followed by adjuvant combined treatment with a platinum and taxane containing chemotherapy, which affords 80% of patients an initial complete response. However, Abdominal and pelvic recurrence rates are high and response to further chemotherapy is limited. Attempts at introducing biologic therapeutic agents to improve outcome in this disease are ongoing, while prognostic or predictive biomarkers that can stratify patients for treatment are still lacking. Using a 60-mer 22K oligonucleotide-based array comparative genome hybridization (CGH) platform combined with DNA isolated from microdissected tumor tissue samples, Birrer et. al. reported that the amplification of 5q31-35.3 in ovarian cancer cells is a negative prognostic indicator for patients with advanced stage high-grade serous ovarian cancer (HGSC). Further studies showed that fibroblast growth factor 1 (FGF1) located in the amplicon, may be one of the driving genes for ovarian cancer progression (Birrer et. al., 2007). Besides FGF1, located on the same amplicon is one of its receptors fibroblast growth factor receptor 4 (FGFR4), suggesting that it may also be amplified and may be another driving gene involved in ovarian cancer pathogenesis.In this study, we used microarrays to explore and compare gene expression profiles between FGFR4 knock down ovarian cancer cell lines and their corresponding parental cell lines. Two high grade serous ovarian cancer cell lines: SKOV3 and OVCA432 were selected for this study. For each of the cell lines, two different siRNA sequences which both target human FGFR4 were used. While a non-target scramble siRNA sequence was used as control. Ovarian cancer cells were transfected with siRNA using lipofectamine (Invitrogen). RNA extraction was performed 72 hours post-transfection, followed by hybridization on Affymetrix microarrays.

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Identification of differentially expressed transcription factors in ovarian cancer

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