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TCGA data ovarian cancer

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https://www.readbyqxmd.com/read/28423358/characterization-of-fusion-genes-in-common-and-rare-epithelial-ovarian-cancer-histologic-subtypes
#1
Madalene A Earp, Rama Raghavan, Qian Li, Junqiang Dai, Stacey J Winham, Julie M Cunningham, Yanina Natanzon, Kimberly R Kalli, Xiaonan Hou, S John Weroha, Paul Haluska, Kate Lawrenson, Simon A Gayther, Chen Wang, Ellen L Goode, Brooke L Fridley
Gene fusions play a critical role in some cancers and can serve as important clinical targets. In epithelial ovarian cancer (EOC), the contribution of fusions, especially by histological type, is unclear. We therefore screened for recurrent fusions in a histologically diverse panel of 220 EOCs using RNA sequencing. The Pipeline for RNA-Sequencing Data Analysis (PRADA) was used to identify fusions and allow for comparison with The Cancer Genome Atlas (TCGA) tumors. Associations between fusions and clinical prognosis were evaluated using Cox proportional hazards regression models...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28350786/methylation-of-mylk3-gene-promoter-region-a-biomarker-to-stratify-surgical-care-in-ovarian-cancer-in-a-multicentre-study
#2
David L Phelps, Jane V Borley, Kirsty J Flower, Roberto Dina, Silvia Darb-Esfahani, Ioana Braicu, Jalid Sehouli, Christina Fotopoulou, Charlotte S Wilhelm-Benartzi, Hani Gabra, Joseph Yazbek, Jayanta Chatterjee, Jacey Ip, Harun Khan, Marina-Therese Likos-Corbett, Robert Brown, Sadaf Ghaem-Maghami
BACKGROUND: Survival benefit from surgical debulking of ovarian cancer (OC) is well established, but some women, despite total macroscopic clearance of disease, still have poor prognosis. We aimed to identify biomarkers to predict benefit from conventional surgery. METHODS: Clinical data from women debulked for high-stage OC were analysed (Hammersmith Hospital, London, UK; 2001-2014). Infinium's HumanMethylation27 array interrogated tumour DNA for differentially methylated CpG sites, correlated to survival, in patients with the least residual disease (RD; Hammersmith Array)...
March 28, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28350120/cross-validation-of-genes-potentially-associated-with-overall-survival-and-drug-resistance-in-ovarian-cancer
#3
Yutao Gao, Xia Liu, Ting Li, Luwei Wei, Antai Yang, Yi Lu, Jian Zhang, Li Li, Sumei Wang, Fuqiang Yin
Ovarian cancer is the leading cause of death among malignancies of the female reproductive system. The 5-year survival rates of ovarian cancer (OC) patients are very poor as a result of recurrent disease and emergence of drug resistance; thus, studies to find predictive markers and factors for drug resistance are ongoing. In the present study, based on the microarrays from The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) profiles covering 1648 OC patients, 11 out of 136 genes that were found to be significantly dysregulated in OC were associated with overall survival (OS) in 489 OC patients of the TCGA cohort...
March 27, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28328815/strobe-compliant-integrin-through-focal-adhesion-involve-in-cancer-stem-cell-and-multidrug-resistance-of-ovarian-cancer
#4
Luwei Wei, Fuqiang Yin, Wei Zhang, Li Li
Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28199976/elf3-is-a-negative-regulator-of-epithelial-mesenchymal-transition-in-ovarian-cancer-cells
#5
Tsz-Lun Yeung, Cecilia S Leung, Kwong-Kwok Wong, Arthur Gutierrez-Hartmann, Joseph Kwong, David M Gershenson, Samuel C Mok
Transcription factors are master switches for various biochemical pathways. However, transcription factors involved in the pathogenesis of ovarian cancer have yet to be explored thoroughly. Therefore, in the present study, we assessed the prognostic value of the transcription factor E74-like factor 3 (ELF3) identified via transcriptome profiling of the epithelial components of microdissected ovarian tumor samples isolated from long- and short-term survivors and determined its roles in ovarian cancer pathogenesis...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28148395/tissue-factor-factor-viia-complex-triggers-protease-activated-receptor-2-dependent-growth-factor-release-and-migration-in-ovarian-cancer
#6
Alice Chanakira, Pamela R Westmark, Irene M Ong, John P Sheehan
OBJECTIVE: Enhanced tissue factor (TF) expression in epithelial ovarian cancer (EOC) is associated with aggressive disease. Our objective was to evaluate the role of the TF-factor VIIa-protease-activated receptor-2 (PAR-2) pathway in human EOC. METHODS: TCGA RNAseq data from EOC databases were analyzed for PAR expression. Cell and microparticle (MP) associated TF protein expression (Western blot) and MP-associated coagulant activity were determined in human EOC (SKOV-3, OVCAR-3 and CaOV-3) and control cell lines...
April 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28118849/distinguishing-potential-bacteria-tumor-associations-from-contamination-in-a-secondary-data-analysis-of-public-cancer-genome-sequence-data
#7
Kelly M Robinson, Jonathan Crabtree, John S A Mattick, Kathleen E Anderson, Julie C Dunning Hotopp
BACKGROUND: A variety of bacteria are known to influence carcinogenesis. Therefore, we sought to investigate if publicly available whole genome and whole transcriptome sequencing data generated by large public cancer genome efforts, like The Cancer Genome Atlas (TCGA), could be used to identify bacteria associated with cancer. The Burrows-Wheeler aligner (BWA) was used to align a subset of Illumina paired-end sequencing data from TCGA to the human reference genome and all complete bacterial genomes in the RefSeq database in an effort to identify bacterial read pairs from the microbiome...
January 25, 2017: Microbiome
https://www.readbyqxmd.com/read/28073598/hdac10-as-a-potential-therapeutic-target-in-ovarian-cancer
#8
Muhtadi M Islam, Tapahsama Banerjee, Colin Z Packard, Shweta Kotian, Karuppaiyah Selvendiran, David E Cohn, Jeffrey D Parvin
OBJECTIVE: We analyzed histone deacetylase 10 (HDAC10) for function in the context of the DNA damage response in BRCA1-null ovarian cancer cells as well as evaluated the potential of general HDAC inhibitors in primary ovarian carcinoma cells. HDAC10 had previously been shown to be highly stimulatory to the process of homology directed repair in HeLa cells, and in this study we investigated whether HDAC10 could impact in vitro the response to anticancer therapies. We hypothesized that the loss of HDAC10 would sensitize cells to platinum therapy...
March 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28049703/pathway-structured-predictive-model-for-cancer-survival-prediction-a-two-stage-approach
#9
Xinyan Zhang, Yan Li, Tomi Akinyemiju, Akinyemi I Ojesina, Phillip Buckhaults, Nianjun Liu, Bo Xu, Nengjun Yi
Heterogeneity in terms of tumor characteristics, prognosis, and survival among cancer patients has been a persistent problem for many decades. Currently, prognosis and outcome predictions are made based on clinical factors and/or by incorporating molecular profiling data. However, inaccurate prognosis and prediction may result by using only clinical or molecular information directly. One of the main shortcomings of past studies is the failure to incorporate prior biological information into the predictive model, given strong evidence of the pathway-based genetic nature of cancer, i...
January 2017: Genetics
https://www.readbyqxmd.com/read/28040436/fam98a-associates-with-ddx1-c14orf166-fam98b-in-a-novel-complex-involved-in-colorectal-cancer-progression
#10
Khondker Ayesha Akter, Mohammed A Mansour, Toshinori Hyodo, Takeshi Senga
Protein Arginine Methyl Transferase 1 (PRMT1) is deemed to be a potential oncogenic protein considering its overexpression in several malignancies including colorectal cancer. However, the molecular pathogenesis regarding PRMT1 overexpression and overall poor patient survival involved in this devastating and life threatening cancer remains obscured. In our previous study, we have identified FAM98A as a novel substrate of PRMT1 and also identified its role in ovarian cancer progression. Here, we showed that the two structural homologs FAM98A and FAM98B included in a novel complex with DDX1 and C14orf166 are required for PRMT1 expression...
December 28, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27980217/the-association-between-copper-transporters-and-the-prognosis-of-cancer-patients-undergoing-chemotherapy-a-meta-analysis-of-literatures-and-datasets
#11
REVIEW
Si Sun, Jing Cai, Qiang Yang, Simei Zhao, Zehua Wang
Copper transporter 1 (CTR1), copper transporter 2 (CTR2), copper-transporting p-type adenosine triphosphatase 1 and 2 (ATP7A and ATP7B) are key mediators of cellular cisplatin, carboplatin and oxaliplatin accumulation. In this meta-analysis, we aimed to evaluate the relation of CTR1, CTR2, ATP7A and ATP7B to overall survival (OS), progression-free survival (PFS), disease-free survival (DFS) and treatment response (TR) of cancer patients who received chemotherapy based on published literatures, the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) datasets...
February 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/27966459/the-transcription-levels-and-prognostic-values-of-seven-proteasome-alpha-subunits-in-human-cancers
#12
Yunhai Li, Jing Huang, Jiazheng Sun, Shili Xiang, Dejuan Yang, Xuedong Ying, Mengqi Lu, Hongzhong Li, Guosheng Ren
Proteasome alpha subunits (PSMAs) have been shown to participate in the malignant progression of human cancers. However, the expression patterns and prognostic values of individual PSMAs remain elusive in most cancers. In the present study, we investigated the mRNA expression levels of seven PSMAs in different kinds of cancers using Oncomine and The Cancer Genome Atlas (TCGA) databases. The prognostic significance of PSMAs was also determined by Kaplan-Meier Plotter and PrognScan databases. Combined with Oncomine and TCGA, the mRNA expression levels of PSMA1-7 were significantly upregulated in breast, lung, gastric, bladder and head and neck cancer compared with normal tissues...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/27868129/identifying-differential-networks-based-on-multi-platform-gene-expression-data
#13
Le Ou-Yang, Hong Yan, Xiao-Fei Zhang
Exploring how the structure of a gene regulatory network differs between two different disease states is fundamental for understanding the biological mechanisms behind disease development and progression. Recently, with rapid advances in microarray technologies, gene expression profiles of the same patients can be collected from multiple microarray platforms. However, previous differential network analysis methods were usually developed based on a single type of platform, which could not utilize the common information shared across different platforms...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27806724/a-network-pathway-based-module-identification-for-predicting-the-prognosis-of-ovarian-cancer-patients
#14
Xin Wang, Shan-Shan Wang, Lin Zhou, Li Yu, Lan-Mei Zhang
BACKGROUND: This study aimed to screen multiple genes biomarkers based on gene expression data for predicting the survival of ovarian cancer patients. METHODS: Two microarray data of ovarian cancer samples were collected from The Cancer Genome Atlas (TCGA) database. The data in the training set were used to construct Reactome functional interactions network, which then underwent Markov clustering, supervised principal components, Cox proportional hazard model to screen significantly prognosis related modules...
November 2, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27799277/the-spike-and-slab-lasso-generalized-linear-models-for-prediction-and-associated-genes-detection
#15
Zaixiang Tang, Yueping Shen, Xinyan Zhang, Nengjun Yi
Large-scale "omics" data have been increasingly used as an important resource for prognostic prediction of diseases and detection of associated genes. However, there are considerable challenges in analyzing high-dimensional molecular data, including the large number of potential molecular predictors, limited number of samples, and small effect of each predictor. We propose new Bayesian hierarchical generalized linear models, called spike-and-slab lasso GLMs, for prognostic prediction and detection of associated genes using large-scale molecular data...
January 2017: Genetics
https://www.readbyqxmd.com/read/27756228/drug-discovery-using-clinical-outcome-based-connectivity-mapping-application-to-ovarian-cancer
#16
Rama Raghavan, Stephen Hyter, Harsh B Pathak, Andrew K Godwin, Gottfried Konecny, Chen Wang, Ellen L Goode, Brooke L Fridley
BACKGROUND: Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer death among women in the United States (5 % of cancer deaths). The standard treatment for patients with advanced EOC is initial debulking surgery followed by carboplatin-paclitaxel combination chemotherapy. Unfortunately, with chemotherapy most patients relapse and die resulting in a five-year overall survival around 45 %. Thus, finding novel therapeutics for treating EOC is essential. Connectivity Mapping (CMAP) has been used widely in cancer drug discovery and generally has relied on cancer cell line gene expression and drug phenotype data...
October 19, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27746113/dna-methylation-regulated-microrna-pathways-in-ovarian-serous-cystadenocarcinoma-a-meta-analysis
#17
David Agustriawan, Chien-Hung Huang, Jim Jinn-Chyuan Sheu, Shan-Chih Lee, Jeffrey J P Tsai, Nilubon Kurubanjerdjit, Ka-Lok Ng
Epigenetic regulation has been linked to the initiation and progression of cancer. Aberrant expression of microRNAs (miRNAs) is one such mechanism that can activate or silence oncogenes (OCGs) and tumor suppressor genes (TSGs) in cells. A growing number of studies suggest that miRNA expression can be regulated by methylation modification, thus triggering cancer development. However, there is no comprehensive in silico study concerning miRNA regulation by direct DNA methylation in cancer. Ovarian serous cystadenocarcinoma (OSC) was therefore chosen as a tumor model for the present work...
October 1, 2016: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/27663592/selective-targeting-of-cyclin-e1-amplified-high-grade-serous-ovarian-cancer-by-cyclin-dependent-kinase-2-and-akt-inhibition
#18
George Au-Yeung, Franziska Lang, Walid J Azar, Chris Mitchell, Kate E Jarman, Kurt Lackovic, Diar Aziz, Carleen Cullinane, Richard B Pearson, Linda Mileshkin, Danny Rischin, Alison M Karst, Ronny Drapkin, Dariush Etemadmoghadam, David D L Bowtell
Purpose: Cyclin E1 (CCNE1) amplification is associated with primary treatment resistance and poor outcome in high-grade serous ovarian cancer (HGSC). Here, we explore approaches to target CCNE1-amplified cancers and potential strategies to overcome resistance to targeted agents.Experimental Design: To examine dependency on CDK2 in CCNE1-amplified HGSC, we utilized siRNA and conditional shRNA gene suppression, and chemical inhibition using dinaciclib, a small-molecule CDK2 inhibitor. High-throughput compound screening was used to identify selective synergistic drug combinations, as well as combinations that may overcome drug resistance...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27649553/inhibition-of-the-nuclear-export-receptor-xpo1-as-a-therapeutic-target-for-platinum-resistant-ovarian-cancer
#19
Ying Chen, Sandra Catalina Camacho, Thomas R Silvers, Albiruni R A Razak, Nashat Y Gabrail, John F Gerecitano, Eva Kalir, Elena Pereira, Brad R Evans, Susan J Ramus, Fei Huang, Nolan Priedigkeit, Estefania Rodriguez, Michael Donovan, Faisal Khan, Tamara Kalir, Robert Sebra, Andrew Uzilov, Rong Chen, Rileen Sinha, Richard Halpert, Jean-Noel Billaud, Sharon Shacham, Dilara McCauley, Yosef Landesman, Tami Rashal, Michael Kauffman, Mansoor R Mirza, Morten Mau-Sørensen, Peter Dottino, John A Martignetti
Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA)...
March 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27569584/the-cd47-don-t-eat-me-signal-is-highly-expressed-in-human-ovarian-cancer
#20
R M Brightwell, K S Grzankowski, S Lele, K Eng, M Arshad, H Chen, K Odunsi
OBJECTIVES: The CD47 "don't eat me" signal allows tumor immune evasion. We tested the association of CD47 expression with outcomes in EOC. METHODS: CD47 expression was examined within the TCGA database for ovarian carcinoma. For validation, IHC was performed on a TMA consisting of specimens from 265 patients with EOC. The medical records of the patients were also retrospectively reviewed to correlate demographic and survival data. RESULTS: CD47 was amplified in 15/316 (5%) ovarian serous cancers in TCGA...
November 2016: Gynecologic Oncology
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