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TCGA data ovarian cancer

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https://www.readbyqxmd.com/read/27868129/identifying-differential-networks-based-on-multi-platform-gene-expression-data
#1
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...
November 21, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27806724/a-network-pathway-based-module-identification-for-predicting-the-prognosis-of-ovarian-cancer-patients
#2
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
#3
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...
October 31, 2016: Genetics
https://www.readbyqxmd.com/read/27756228/drug-discovery-using-clinical-outcome-based-connectivity-mapping-application-to-ovarian-cancer
#4
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
#5
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
#6
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. EXPERIMENT DESIGN: To examine dependency on CDK2 in CCNE1 amplified HGSC, we utilised siRNA and conditional shRNA gene suppression, and chemical inhibition using dinaciclib, a small molecule CDK2 inhibitor...
September 23, 2016: 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
#7
John A Martignetti, Ying Chen, 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 M Khan, Tamara Kalir, Robert P 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
PURPOSE: Ovarian cancer's (OvCa) high fatality-to-case ratio 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 OvCa. EXPERIMENTAL DESIGN: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO data sets and tissue microarrays (TMAs)...
September 20, 2016: 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
#8
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
https://www.readbyqxmd.com/read/27561551/integrative-proteomic-profiling-of-ovarian-cancer-cell-lines-reveals-precursor-cell-associated-proteins-and-functional-status
#9
F Coscia, K M Watters, M Curtis, M A Eckert, C Y Chiang, S Tyanova, A Montag, R R Lastra, E Lengyel, M Mann
A cell line representative of human high-grade serous ovarian cancer (HGSOC) should not only resemble its tumour of origin at the molecular level, but also demonstrate functional utility in pre-clinical investigations. Here, we report the integrated proteomic analysis of 26 ovarian cancer cell lines, HGSOC tumours, immortalized ovarian surface epithelial cells and fallopian tube epithelial cells via a single-run mass spectrometric workflow. The in-depth quantification of >10,000 proteins results in three distinct cell line categories: epithelial (group I), clear cell (group II) and mesenchymal (group III)...
August 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27536319/gene-coexpression-analyses-differentiate-networks-associated-with-diverse-cancers-harboring-tp53-missense-or-null-mutations
#10
Kathleen Oros Klein, Karim Oualkacha, Marie-Hélène Lafond, Sahir Bhatnagar, Patricia N Tonin, Celia M T Greenwood
In a variety of solid cancers, missense mutations in the well-established TP53 tumor suppressor gene may lead to the presence of a partially-functioning protein molecule, whereas mutations affecting the protein encoding reading frame, often referred to as null mutations, result in the absence of p53 protein. Both types of mutations have been observed in the same cancer type. As the resulting tumor biology may be quite different between these two groups, we used RNA-sequencing data from The Cancer Genome Atlas (TCGA) from four different cancers with poor prognosis, namely ovarian, breast, lung and skin cancers, to compare the patterns of coexpression of genes in tumors grouped according to their TP53 missense or null mutation status...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27496093/a-brca1-2-mutational-signature-and-survival-in-ovarian-high-grade-serous-carcinoma
#11
Fei Dong, Phani K Davineni, Brooke E Howitt, Andrew H Beck
BACKGROUND: Mutational signatures have been identified by the broad sequencing of cancer genomes and reflect underlying processes of mutagenesis. The clinical application of mutational signatures is not well defined. Here we aim to assess the prognostic utility of mutational signatures in ovarian high-grade serous carcinoma. METHODS: Open access data of 15,439 somatic mutations of 310 ovarian high-grade serous carcinomas from The Cancer Genome Atlas (TCGA) are used to construct a Bayesian model to classify each cancer as either having or lacking a BRCA1/2 mutational signature...
August 5, 2016: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/27493999/integration-of-multi-modal-biomedical-data-to-predict-cancer-grade-and-patient-survival
#12
John H Phan, Ryan Hoffman, Sonal Kothari, Po-Yen Wu, May D Wang
The Big Data era in Biomedical research has resulted in large-cohort data repositories such as The Cancer Genome Atlas (TCGA). These repositories routinely contain hundreds of matched patient samples for genomic, proteomic, imaging, and clinical data modalities, enabling holistic and multi-modal integrative analysis of human disease. Using TCGA renal and ovarian cancer data, we conducted a novel investigation of multi-modal data integration by combining histopathological image and RNA-seq data. We compared the performances of two integrative prediction methods: majority vote and stacked generalization...
February 2016: ... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics
https://www.readbyqxmd.com/read/27478503/joint-analysis-of-multiple-high-dimensional-data-types-using-sparse-matrix-approximations-of-rank-1-with-applications-to-ovarian-and-liver-cancer
#13
Gordon Okimoto, Ashkan Zeinalzadeh, Tom Wenska, Michael Loomis, James B Nation, Tiphaine Fabre, Maarit Tiirikainen, Brenda Hernandez, Owen Chan, Linda Wong, Sandi Kwee
BACKGROUND: Technological advances enable the cost-effective acquisition of Multi-Modal Data Sets (MMDS) composed of measurements for multiple, high-dimensional data types obtained from a common set of bio-samples. The joint analysis of the data matrices associated with the different data types of a MMDS should provide a more focused view of the biology underlying complex diseases such as cancer that would not be apparent from the analysis of a single data type alone. As multi-modal data rapidly accumulate in research laboratories and public databases such as The Cancer Genome Atlas (TCGA), the translation of such data into clinically actionable knowledge has been slowed by the lack of computational tools capable of analyzing MMDSs...
2016: BioData Mining
https://www.readbyqxmd.com/read/27465871/-identification-and-prognostic-value-of-differentially-expressed-proteins-of-patients-with-platinum-resistance-epithelial-ovarian-cancer-in-serum
#14
W J Wu, Q Wang, W Zhang, L Li
OBJECTIVE: To identified differentially expressed proteins associated with platinum resistance in platinum resistance epithelial oarian cancer(EOC)patients in serum and investigate their clinical value. METHODS: A total of 106 patients withoverian tumor in affiliated tumor hospital of Guangxi Medical University from August 1998 to September 2013 were enrolled in this study, which include 52 cases od platinum-sensitive(PTS), 44 cases of platinum-resistant(PTR)and 10 cases of benign ovarian cyst(BOC)...
July 25, 2016: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/27453446/allele-specific-quantification-of-structural-variations-in-cancer-genomes
#15
Yang Li, Shiguo Zhou, David C Schwartz, Jian Ma
Aneuploidy and structural variations (SVs) generate cancer genomes containing a mixture of rearranged genomic segments with extensive somatic copy number alterations. However, existing methods can identify either SVs or allele-specific copy number alterations but not both simultaneously, which provides a limited view of cancer genome structure. Here, we introduce Weaver, an algorithm for the quantification and analysis of allele-specific copy numbers of SVs. Weaver uses a Markov random field to estimate joint probabilities of allele-specific copy numbers of SVs and their inter-connectivity based on paired-end whole-genome sequencing data...
July 2016: Cell Systems
https://www.readbyqxmd.com/read/27444036/panobinostat-sensitizes-cyclin-e-high-homologous-recombination-proficient-ovarian-cancer-to-olaparib
#16
Andrew J Wilson, Kofi Sarfo-Kantanka, Toby Barrack, Alexandra Steck, Jeanette Saskowski, Marta A Crispens, Dineo Khabele
OBJECTIVE: Homologous recombination (HR) proficient ovarian cancers, including CCNE1 (cyclin E)-amplified tumors, are resistant to poly (ADP-ribose) polymerase inhibitors (PARPi). Histone deacetylase inhibitors (HDACi) are effective in overcoming tumor resistance to DNA damaging drugs. Our goal was to determine whether panobinostat, a newly FDA-approved HDACi, can sensitize cyclin E, HR-proficient ovarian cancer cells to the PARPi olaparib. METHODS: Expression levels of CCNE1 (cyclin E), BRCA1, RAD51 and E2F1 in ovarian tumors and cell lines were extracted from The Cancer Genome Atlas (TCGA) and Broad-Novartis Cancer Cell Line Encyclopedia (CCLE)...
October 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27381624/the-doppelg%C3%A3-nger-effect-hidden-duplicates-in-databases-of-transcriptome-profiles
#17
Levi Waldron, Markus Riester, Marcel Ramos, Giovanni Parmigiani, Michael Birrer
Whole-genome analysis of cancer specimens is commonplace, and investigators frequently share or re-use specimens in later studies. Duplicate expression profiles in public databases will impact re-analysis if left undetected, a so-called "doppelgänger" effect. We propose a method that should be routine practice to accurately match duplicate cancer transcriptomes when nucleotide-level sequence data are unavailable, even for samples profiled by different microarray technologies or by both microarray and RNA sequencing...
November 2016: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/27372738/integrated-proteogenomic-characterization-of-human-high-grade-serous-ovarian-cancer
#18
Hui Zhang, Tao Liu, Zhen Zhang, Samuel H Payne, Bai Zhang, Jason E McDermott, Jian-Ying Zhou, Vladislav A Petyuk, Li Chen, Debjit Ray, Shisheng Sun, Feng Yang, Lijun Chen, Jing Wang, Punit Shah, Seong Won Cha, Paul Aiyetan, Sunghee Woo, Yuan Tian, Marina A Gritsenko, Therese R Clauss, Caitlin Choi, Matthew E Monroe, Stefani Thomas, Song Nie, Chaochao Wu, Ronald J Moore, Kun-Hsing Yu, David L Tabb, David Fenyö, Vineet Bafna, Yue Wang, Henry Rodriguez, Emily S Boja, Tara Hiltke, Robert C Rivers, Lori Sokoll, Heng Zhu, Ie-Ming Shih, Leslie Cope, Akhilesh Pandey, Bing Zhang, Michael P Snyder, Douglas A Levine, Richard D Smith, Daniel W Chan, Karin D Rodland
To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival...
July 28, 2016: Cell
https://www.readbyqxmd.com/read/27198045/glycosyltransferase-gene-expression-profiles-classify-cancer-types-and-propose-prognostic-subtypes
#19
Jahanshah Ashkani, Kevin J Naidoo
Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27190995/wwox-cnv-67048-functions-as-a-risk-factor-for-epithelial-ovarian-cancer-in-chinese-women-by-negatively-interacting-with-oral-contraceptive-use
#20
Yongxiu Chen, Xiaochang Tan, Yongli Ding, Bi Mai, Xiaowen Huang, Guiying Hu, Xiping Luo
Copy number variations (CNVs) have attracted increasing evidences to represent their roles as cancer susceptibility regulators. However, little is known about the role of CNV in epithelia ovarian cancer (EOC). Recently, the CNV-67048 of WW domain-containing oxidoreductase (WWOX) was reported to alter cancer risks. Considering that WWOX also plays a role in EOC, we hypothesized that the CNV-67048 was associated with EOC risk. In a case-control study of 549 EOC patients and 571 age (±5 years) matched cancer-free controls, we found that the low copy number of CNV-67048 (1-copy and 0-copy) conferred a significantly increased risk of EOC (OR = 1...
2016: BioMed Research International
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