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Tcga data ovarian cancer platinum resistance

V Heinzelmann-Schwarz, A Knipprath Mészaros, S Stadlmann, F Jacob, A Schoetzau, K Russell, M Friedlander, G Singer, M Vetter
OBJECTIVES: Endocrine therapy is used as maintenance in estrogen receptor (ER) positive breast cancers and has been proposed in low-grade serous ovarian cancers (LGSOC). Here we examine a rationale for its use as maintenance in high-grade serous ovarian cancers (HGSOC). METHODS: We accessed the TCGA PANCAN dataset to evaluate the expression of ESR1. ESR1 expression data on all cancers (n=8901) and HGSOC (n=527) were followed by investigation of ER expression via immunohistochemistry (IHC) (n=4071)...
January 2018: Gynecologic Oncology
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
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
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
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
Meng Zhou, Yanying Sun, Yifan Sun, Wanying Xu, Zhaoyue Zhang, Hengqiang Zhao, Zhaohua Zhong, Jie Sun
There is growing evidence of dysregulated long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic efforts of searching for an expression-based lncRNA signature for prognosis prediction in ovarian cancer (OvCa) have not been made yet. Here, we performed comprehensive analysis for lncRNA expression profiles and clinical data of 544 OvCa patients from The Cancer Genome Atlas (TCGA), and identified an eight-lncRNA signature with ability to classify patients of the training cohort into high-risk group showing poor outcome and low-risk group showing significantly improved outcome, which was further validated in the validation cohort and entire TCGA cohort...
May 31, 2016: Oncotarget
Kevin H Eng, Bret M Hanlon, William H Bradley, J Brian Szender
OBJECTIVES: While primary treatment for high-grade serous ovarian cancer tends to be uniform - maximal debulking and platinum/taxane adjuvant chemotherapy - there is little standardization of treatment in the recurrent setting beyond the exhaustive use of platinum therapies. Using secondary data from multiple centers participating in the Cancer Genome Atlas study (TCGA), we seek to characterize clinical features, timing and serial response data to provide empirical evidence for treatment expectations in the recurrent setting...
November 2015: Gynecologic Oncology
Jeyshka M Reyes-González, Guillermo N Armaiz-Peña, Lingegowda S Mangala, Fatma Valiyeva, Cristina Ivan, Sunila Pradeep, Ileabett M Echevarría-Vargas, Adrian Rivera-Reyes, Anil K Sood, Pablo E Vivas-Mejía
The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared with their cisplatin-sensitive counterparts...
October 2015: Molecular Cancer Therapeutics
Shaojun Zhang, Yuan Yuan, Dapeng Hao
Detecting mutation in BRCA1/2 is a generally accepted strategy for screening ovarian cancers that have impaired homologous recombination (HR) ability and improved sensitivity to PARP inhibitor. However, a substantial subset of BRCA-mutant ovarian cancer patients shows less impaired or unimpaired HR ability, resulting in nonequivalent outcome after ovarian cancer development. We hypothesize that genomic instability provides a lifetime record of DNA repair deficiency and predicts ovarian cancer outcome. Based on the multi-dimensional TCGA ovarian cancer data, we developed a biological rationale-driven genomic instability score integrating somatic mutation and copy number change in a tumor genome...
2014: PloS One
Pavla Brachova, Samuel R Mueting, Matthew J Carlson, Michael J Goodheart, Anna M Button, Sarah L Mott, Donghai Dai, Kristina W Thiel, Eric J Devor, Kimberly K Leslie
Individual mutations in the tumor suppressor TP53 alter p53 protein function. Some mutations create a non-functional protein, whereas others confer oncogenic activity, which we term 'oncomorphic'. Since mutations in TP53 occur in nearly all ovarian tumors, the objective of this study was to determine the relationship of oncomorphic TP53 mutations with patient outcomes in advanced serous ovarian cancer patients. Clinical and molecular data from 264 high-grade serous ovarian cancer patients uniformly treated with standard platinum- and taxane-based adjuvant chemotherapy were downloaded from The Cancer Genome Atlas (TCGA) portal...
February 2015: International Journal of Oncology
Evelyn Despierre, Matthieu Moisse, Betül Yesilyurt, Jalid Sehouli, Ioana Braicu, Sven Mahner, Dan Cacsire Castillo-Tong, Robert Zeillinger, Sandrina Lambrechts, Karin Leunen, Frédéric Amant, Philippe Moerman, Diether Lambrechts, Ignace Vergote
OBJECTIVE: Platinum resistance remains an obstacle in the treatment of epithelial ovarian cancer (EOC). The goal of this study was to profile EOCs for somatic copy number alterations (SCNAs) as predictive markers of platinum response. METHODS: SCNAs were assessed in a discovery (n=86) and validation cohort (n=115) of high risk stage I or stage II-IV EOCs using high-resolution SNP arrays. ASCAT and GISTIC identified all significantly overrepresented amplified or deleted chromosomal regions...
December 2014: Gynecologic Oncology
Samantha Cohen, Rebecca Mosig, Erin Moshier, Elena Pereira, Jamal Rahaman, Monica Prasad-Hayes, Richard Halpert, Jean-Noel Billaud, Peter Dottino, John A Martignetti
OBJECTIVE: High-grade serous ovarian cancer (HGSOC) that is resistant to platinum-based chemotherapy has a particularly poor prognosis. Response to platinum has both prognostic survival value and dictates secondary treatment strategies. Using transcriptome analysis, we sought to identify differentially expressed genes/pathways based on a tumor's platinum response for discovering novel predictive biomarkers. METHODS: Seven primary HGSOC tumor samples, representing two extremes of platinum sensitivity/timing of disease recurrence, were analyzed by RNA-Seq, Ingenuity Pathways Analysis (IPA) and Upstream Regulator Analysis (URA), and used to explore differentially expressed genes and prevalent molecular and cellular processes...
September 2014: Gynecologic Oncology
Kazimierz O Wrzeszczynski, Vinay Varadan, Sitharthan Kamalakaran, Douglas A Levine, Nevenka Dimitrova, Robert Lucito
The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to discover genes critical to the development, progression, and therapeutic resistance of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatics analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor...
2013: Methods in Molecular Biology
Yong Han, Hao Huang, Zhen Xiao, Wei Zhang, Yanfei Cao, Like Qu, Chengchao Shou
PURPOSE: This study aims to explore gene expression signatures and serum biomarkers to predict intrinsic chemoresistance in epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Gene expression profiling data of 322 high-grade EOC cases between 2009 and 2010 in The Cancer Genome Atlas project (TCGA) were used to develop and validate gene expression signatures that could discriminate different responses to first-line platinum/paclitaxel-based treatments. A gene regulation network was then built to further identify hub genes responsible for differential gene expression between the complete response (CR) group and the progressive disease (PD) group...
2012: PloS One
Joyce N Barlin, Petar Jelinic, Narciso Olvera, Faina Bogomolniy, Maria Bisogna, Fanny Dao, Richard R Barakat, Dennis S Chi, Douglas A Levine
OBJECTIVES: High-grade serous ovarian cancer (HGSOC) mostly presents at an advanced stage and has a low overall survival rate. However, a subgroup of patients are seemingly cured after standard initial therapy. We hypothesize that the molecular profiles of these patients vary from long-term survivors who recur. METHODS: Patients with advanced HGSOC who underwent primary cytoreductive surgery and platinum-based chemotherapy were identified from The Cancer Genome Atlas (TCGA) and institutional (MSKCC) samples...
March 2013: Gynecologic Oncology
Insuk Sohn, Woon Yong Jung, Chang Ohk Sung
OBJECTIVE: The standard treatment for high grade ovarian serous cancer (HG-OSC) is aggressive cytoreductive surgery followed by platinum based chemotherapy. However, approximately 30% of patients exhibit platinum resistance, and those patients show aggressive clinical courses. Currently, it is difficult to predict which HG-OSC patients will respond to platinum-based chemotherapy. METHODS: We analyzed whole exome sequences for 174 HG-SOC patients using data obtained from The Cancer Genome Atlas (TCGA) data portal regarding platinum response...
July 2012: Gynecologic Oncology
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