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Tcga bladder

Hossein Tezval, Natalia Dubrowinskaja, Inga Peters, Christel Reese, Katrin Serth, Faranaz Atschekzei, Jörg Hennenlotter, Arnulf Stenzl, Markus A Kuczyk, Jürgen Serth
The relevance of Corticotropin Releasing Hormone (CRH)-system in human malignancies is a question of growing interest. Here we investigated hypermethylation and epigenetic silencing of the CRH-Binding Protein (CRHBP) gene in clear cell renal cell cancer (ccRCC). Relative methylation of the CRHBP CpG island (CGI) was determined in 17 tumor cell lines as well as 86 ccRCC samples and 66 paired normal tissues using pyrosequencing and quantitative methylation specific PCR of bisulfite converted DNA. Results were statistically compared with relative mRNA expression levels of CRHBP and clinicopathological parameters of patients...
2016: PloS One
Philipp H Baldia, Angela Maurer, Timon Heide, Michael Rose, Robert Stoehr, Arndt Hartmann, Sarah V Williams, Margaret A Knowles, Ruth Knuechel, Nadine T Gaisa
Although drugable fibroblast growth factor receptor (FGFR) alterations in squamous cell carcinomas (SCC) of various entities are well known, little is known about FGFR modifications in squamous differentiated bladder cancer. Therefore, our study evaluated FGFR1-3 alterations as a putative therapeutic target in this subgroup. We analyzed 73 squamous differentiated bladder cancers (n = 10 pT2, n = 55 pT3, n = 8 pT4) for FGFR1-3 protein expression, FGFR1-3 copy number variations, FGFR3 chromosomal rearrangements (fluorescence in situ hybridization (FISH)) and FGFR3 mutations (SNapShot analysis)...
September 22, 2016: Oncotarget
Ayman Oweida, Shilpa Bhatia, Kellen Hirsch, Dylan Calame, Anastacia Griego, Steve Keysar, Todd Pitts, Jaspreet Sharma, Gail Eckhardt, Antonio Jimeno, Xiao Jing Wang, Gill Parkash, Joseph Califano, Sana Karam
Ephrin B2 is variably expressed on tumor cells and its blockade has been shown to inhibit angiogenesis in animal models of pancreatic, colorectal, lung and head and neck squamous cell carcinomas. However, the implications of ephrinB2 expression in cancer patients have remained elusive. In this study, we analyzed the cancer genome atlas (TCGA) for ephrinB2 expression. We report significant correlations between EFNB2 expression, overall survival and disease-free survival in head and neck squamous cell carcinoma (HNSCC, n = 519), pancreatic adenocarcinoma (n = 186) and bladder urothelial carcinoma (n = 410)...
September 20, 2016: Molecular Carcinogenesis
Vipulkumar Dadhania, Miao Zhang, Li Zhang, Jolanta Bondaruk, Tadeusz Majewski, Arlene Siefker-Radtke, Charles C Guo, Colin Dinney, David E Cogdell, Shizhen Zhang, Sangkyou Lee, June G Lee, John N Weinstein, Keith Baggerly, David McConkey, Bogdan Czerniak
BACKGROUND: It has been suggested that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to chemotherapy. We aimed to validate these subtypes in several clinical cohorts and identify signature immunohistochemical markers that would permit simple and cost-effective classification of the disease in primary care centers. METHODS: We analyzed genomic expression profiles of bladder cancer in three cohorts of fresh frozen tumor samples: MD Anderson (n=132), Lund (n=308), and The Cancer Genome Atlas (TCGA) (n=408) to validate the expression signatures of luminal and basal subtypes and relate them to clinical follow-up data...
August 25, 2016: EBioMedicine
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
M L Nickerson, N Witte, K M Im, S Turan, C Owens, K Misner, S X Tsang, Z Cai, S Wu, M Dean, J C Costello, D Theodorescu
The utility of tumor-derived cell lines is dependent on their ability to recapitulate underlying genomic aberrations and primary tumor biology. Here, we sequenced the exomes of 25 bladder cancer (BCa) cell lines and compared mutations, copy number alterations (CNAs), gene expression and drug response to BCa patient profiles in The Cancer Genome Atlas (TCGA). We observed a mutation pattern associated with altered CpGs and APOBEC-family cytosine deaminases similar to mutation signatures derived from somatic alterations in muscle-invasive (MI) primary tumors, highlighting a major mechanism(s) contributing to cancer-associated alterations in the BCa cell line exomes...
June 6, 2016: Oncogene
Leandro M Colli, Mitchell J Machiela, Timothy A Myers, Lea Jessop, Kai Yu, Stephen J Chanock
Immune checkpoint inhibitor treatment represents a promising approach toward treating cancer and has been shown to be effective in a subset of melanoma, non-small cell lung cancer (NSCLC), and kidney cancers. Recent studies have suggested that the number of nonsynonymous mutations (NsM) can be used to select melanoma and NSCLC patients most likely to benefit from checkpoint inhibitor treatment. It is hypothesized that a higher burden of NsM generates novel epitopes and gene products, detected by the immune system as foreign...
July 1, 2016: Cancer Research
Hanwei Zhang, Kris Prado, Kelvin X Zhang, Elizabeth M Peek, Jane Lee, Xiaoyan Wang, Jiaoti Huang, Gang Li, Matteo Pellegrini, Arnold I Chin
PURPOSE: The transcriptional regulation mediating cancer cell differentiation into distinct molecular subtypes and modulating sensitivity to existing treatments is an enticing therapeutic target. Our objective was to characterize the ability of the forkhead/winged transcription factor FOXP3 to modulate the differentiation of bladder cancer. EXPERIMENTAL DESIGN: Expression of FOXP3 was analyzed by immunohistochemistry in a tumor microarray of 587 samples and overall survival in a subset of 187 patients following radical cystectomy...
May 17, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Shenghua Liu, Yishuo Wu, Tian Yang, Chenchen Feng, Haowen Jiang
The amplification of YWHAZ was commonly seen in bladder cancer. We explore the biological significance of YWHAZ amplification on bladder cancer, and the correlation with important other molecular events. The Cancer Genome Atlas (TCGA) database was exploited to study the impact of YWHAZ amplification on either CDKN2A or TP53 mutations. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was also exploited to clustering of enriched genes in the cBioPortal Enrichment tests. There were 127 cases with available mutation and CNV data in the corresponding TCGA bladder cancer dataset, 20% of them had YWHAZ alteration...
June 7, 2016: Oncotarget
Jan Budczies, Michael Bockmayr, Carsten Denkert, Frederick Klauschen, Stefan Gröschel, Silvia Darb-Esfahani, Nicole Pfarr, Jonas Leichsenring, Maristela L Onozato, Jochen K Lennerz, Manfred Dietel, Stefan Fröhling, Peter Schirmacher, A John Iafrate, Wilko Weichert, Albrecht Stenzinger
Inhibition of the PD-L1 (CD274) - PD-1 axis has emerged as a powerful cancer therapy that prevents evasion of tumor cells from the immune system. While immunohistochemical detection of PD-L1 was introduced as a predictive biomarker with variable power, much less is known about copy number alterations (CNA) affecting PD-L1 and their associations with expression levels, mutational load, and survival. To gain insight, we employed The Cancer Genome Atlas (TCGA) datasets to comprehensively analyze 22 major cancer types for PD-L1 CNAs...
August 2016: Genes, Chromosomes & Cancer
Qingdi Quentin Li, Jian-Jiang Hao, Zheng Zhang, Iawen Hsu, Yi Liu, Zhen Tao, Keidren Lewi, Adam R Metwalli, Piyush K Agarwal
The Cancer Genome Atlas (TCGA) project recently identified the importance of mutations in chromatin remodeling genes in human carcinomas. These findings imply that epigenetic modulators might have a therapeutic role in urothelial cancers. To exploit histone deacetylases (HDACs) as targets for cancer therapy, we investigated the HDAC inhibitors (HDACIs) romidepsin, trichostatin A, and vorinostat as potential chemotherapeutic agents for bladder cancer. We demonstrate that the three HDACIs suppressed cell growth and induced cell death in the bladder cancer cell line 5637...
June 2016: International Journal of Oncology
Chen-Min Sun, Da-Bo Xiong, Yang Yan, Jiang Geng, Min Liu, Xu-Dong Yao
AIMS: Metabolic alterations in cancer, including bladder cancer, have been addressed in recent years. We aimed to study the role of phosphofructokinase (PFK) in muscle-invasive bladder cancer (MIBC). METHOD: By in silico analysis of the bladder cancer data from the Cancer Genome Atlas (TCGA) database using the cBioPortal platform, we studied genetic alteration of genes within the PFK family (PFKL, PFKM, PFKP, PFKFB1, PFKFB2, PFKFB3, and PFKFB4). In vitro studies were carried out using the PFK inhibitor 2,5-anhydro-D-glucitol-6-phosphate...
2016: International Journal of Biological Markers
Thomas R Gill, Mohammad D Samy, Shanitra N Butler, James A Mauro, Wade J Sexton, George Blanck
Tumor immunoscoring is rapidly becoming a universal parameter of prognosis, and T-cells isolated from tumor masses are used for ex vivo amplification and readministration to patients to facilitate an antitumor immune response. We recently exploited the cancer genome atlas (TCGA) RNASeq data to assess T-cell receptor (TcR) expression and, in particular, discovered strong correlations between major histocompatibility class II (MHCII) and TcR-α constant region expression levels. In this article, we describe the results of searching TCGA exome files for TcR-α V-regions, followed by searching the V-region datasets for TcR-α-J regions...
2016: Cancer Informatics
Friedrich-Carl von Rundstedt, Kimal Rajapakshe, Jing Ma, James M Arnold, Jie Gohlke, Vasanta Putluri, Rashmi Krishnapuram, D Badrajee Piyarathna, Yair Lotan, Daniel Gödde, Stephan Roth, Stephan Störkel, Jonathan M Levitt, George Michailidis, Arun Sreekumar, Seth P Lerner, Cristian Coarfa, Nagireddy Putluri
PURPOSE: We used targeted mass spectrometry to study the metabolic fingerprint of urothelial cancer and determine whether the biochemical pathway analysis gene signature would have a predictive value in independent cohorts of patients with bladder cancer. MATERIALS AND METHODS: Pathologically evaluated, bladder derived tissues, including benign adjacent tissue from 14 patients and bladder cancer from 46, were analyzed by liquid chromatography based targeted mass spectrometry...
June 2016: Journal of Urology
Xinsen Xu, Lei Zhou, Runchen Miao, Wei Chen, Yanyan Zhou, Qing Pang, Kai Qu, Chang Liu
Although overweight and obesity increase cancer risk, it is still controversial with respect to cancer mortality. In the current study, we enrolled 2670 patients of 14 tumor types from the Cancer Genome Atlas (TCGA) project, to identify the prognostic role of overweight and obesity in cancer patients. After dividing the patients into different groups by the body mass index (BMI), we found significant lower mortality in the obesity group. In addition, we also treat BMI value as a binary categorical variable or continuous variable, respectively...
January 26, 2016: Oncotarget
Silvia Pineda, Francisco X Real, Manolis Kogevinas, Alfredo Carrato, Stephen J Chanock, Núria Malats, Kristel Van Steen
Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we propose a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm...
December 2015: PLoS Genetics
Alice Cavanaugh, Brendon Juengst, Kathleen Sheridan, John F Danella, Heinric Williams
Heat shock protein 90 (HSP90) plays a critical role in the survival of cancer cells including muscle invasive bladder cancer (MIBC). The addiction of tumor cells to HSP90 has promoted the development of numerous HSP90 inhibitors and their use in clinical trials. This study evaluated the role of inhibiting HSP90 using STA9090 (STA) alone or in combination with the HSP70 inhibitor VER155008 (VER) in several human MIBC cell lines. While both STA and VER inhibited MIBC cell growth and migration and promoted apoptosis, combination therapy was more effective...
November 24, 2015: Oncotarget
Yang Gao, Kaijie Wu, Yule Chen, Jiancheng Zhou, Chong Du, Qi Shi, Shan Xu, Jing Jia, Xiaoshuang Tang, Feng Li, Ke Hui, Dalin He, Peng Guo
Abundant evidence has demonstrated critical roles of KLF5 in regulating cell proliferation in various cancers, however, its additional roles in other aspects of cancer development remain to be further clarified. In this study, we found that KLF5 was essential for cancer cell-endothelial cell interaction in vitro and tumor angiogenesis in nude mice based on lentivirus-mediated KLF5 knockdown bladder cancer cell models. Moreover, KLF5 insufficiency abolished the ability of bladder cancer cells to induce neovascularization in rabbit cornea...
December 22, 2015: Oncotarget
Haibing Xiao, Kun Tang, Peijun Liu, Ke Chen, Junhui Hu, Jin Zeng, Wei Xiao, Gan Yu, Weiming Yao, Hui Zhou, Heng Li, Yingtian Pan, Anping Li, Zhangqun Ye, Ji Wang, Hua Xu, Qihong Huang
Long non-coding RNA (lncRNAs) play a critical role in the development of cancers. LncRNA metastasis-associated lung adenocarcinoma transcript 1(MALAT1) has recently been identified to be involved in tumorigenesis of several cancers such as lung cancer, bladder cancer and so on. Here, we found that MALAT1 exist a higher fold change (Tumor/Normal) in clear cell kidney carcinoma (KIRC) from The Cancer Genome Atlas (TCGA) Data Portal and a negative correlation with miR-200s family. We further demonstrated MALAT1 promote KIRC proliferation and metastasis through sponging miR-200s in vitro and in vivo...
November 10, 2015: Oncotarget
Mónica Martínez-Fernández, Andrew Feber, Marta Dueñas, Cristina Segovia, Carolina Rubio, Maria Fernandez, Felipe Villacampa, José Duarte, Fernando F López-Calderón, Ma José Gómez-Rodriguez, Daniel Castellano, Jose L Rodriguez-Peralto, Federico de la Rosa, Stephan Beck, Jesús M Paramio
BACKGROUND: Long non-coding RNAs (lncRNAs) have been claimed as key molecular players in gene expression regulation, being involved in diverse epigenetic processes. They are aberrantly expressed in various tumors, but their exact role in bladder cancer is still obscure. We have recently found a major role of the Polycomb repression complex in recurrence of non-muscle-invasive bladder cancer. Here, we report the xpression of Polycomb-related lncRNAs:antisense noncoding RNA in the INK4 locus (ANRIL) and HOX antisense intergenic RNA (HOTAIR) in these tumors...
2015: Clinical Epigenetics
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