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Tcga prostate

Juan C Rodriguez, Germán A González, Cristóbal Fresno, Andrea S Llera, Elmer A Fernández
Transcriptome analysis is essential to understand the mechanisms regulating key biological processes and functions. The first step usually consists of identifying candidate genes; to find out which pathways are affected by those genes, however, functional analysis (FA) is mandatory. The most frequently used strategies for this purpose are Gene Set and Singular Enrichment Analysis (GSEA and SEA) over Gene Ontology. Several statistical methods have been developed and compared in terms of computational efficiency and/or statistical appropriateness...
September 24, 2016: Computers in Biology and Medicine
Emily Eva Holmes, Diane Goltz, Verena Sailer, Maria Jung, Sebastian Meller, Barbara Uhl, Jörn Dietrich, Magda Röhler, Jörg Ellinger, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation (mPITX3) and its potential role as a prognostic biomarker were investigated. Furthermore, mPITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 (mPITX2)...
2016: Clinical Epigenetics
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
Sebastian Meller, Lisa Zipfel, Heidrun Gevensleben, Jörn Dietrich, Jörg Ellinger, Michael Majores, Johannes Stein, Verena Sailer, Maria Jung, Glen Kristiansen, Dimo Dietrich
Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR...
September 30, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Johannes Brägelmann, Niklas Klümper, Anne Offermann, Anne von Mässenhausen, Diana Böhm, Mario Deng, Angela Queisser, Christine Sanders, Isabella Syring, Axel S Merseburger, Wenzel Vogel, Elisabeth Sievers, Ignacija Vlasic, Jessica Carlsson, Ove Andrén, Peter Brossart, Stefan Duensing, Maria A Svensson, Zaki Shaikhibrahim, Jutta Kirfel, Sven Perner
PURPOSE: The Mediator complex is a multi-protein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Since gene expression is frequently altered in cancer a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches. EXPERIMENTAL DESIGN: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n=8568) using data from The Cancer Genome Atlas (TCGA)...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Milan S Geybels, Jonathan L Wright, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Shanshan Zhao, Ziding Feng, Elaine A Ostrander, Daniel W Lin, Peter S Nelson, Janet L Stanford
BACKGROUND: Identifying the subset of patients with clinically localized prostate cancer (PCa) at the highest risk of recurrence remains challenging, and better prognostic markers are needed. Gleason score is the best predictor of PCa aggressiveness and prognosis. In the present study, we generated an epigenetic signature based on high versus low Gleason score tumors and evaluated its ability to predict recurrence after radical prostatectomy. METHODS: Genome-wide DNA methylation data from The Cancer Genome Atlas (TCGA; no...
2016: Clinical Epigenetics
Martin Schlensog, Lara Magnus, Timon Heide, Julian Eschenbruch, Florian Steib, Maximilian Tator, Vera Kloten, Michael Rose, Erik Noetzel, Nadine T Gaisa, Ruth Knüchel, Edgar Dahl
Secreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA)...
September 13, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Gautier Stoll, Kristina Iribarren, Judith Michels, Alexandra Leary, Laurence Zitvogel, Isabelle Cremer, Guido Kroemer
Loss of expression of calreticulin (CALR) has been detected by immunohistochemistry in a fraction of non-small cell lung cancers (NSCLC) and has been demonstrated to have a major negative prognostic impact on overall patient survival. Here, we analyzed the impact of CALR expression levels detected by microarray finding a positive correlation between CALR and the expression of a metagene indicating the presence of cytotoxic T lymphocytes (CTL) in NSCLC and ovarian cancer. In addition, we detected a positive correlation with a metagene suggestive of activated dendritic cell (aDC) infiltration in ovarian cancer...
July 2016: Oncoimmunology
Xuechao Wan, Wenhua Huang, Shu Yang, Yalong Zhang, Honglei Pu, Fangqiu Fu, Yan Huang, Hai Wu, Tao Li, Yao Li
Prostate cancer (PCa) is a leading cause of mortality among males. Long non-coding RNAs (lncRNAs) are subclass of noncoding RNAs that may act as biomarkers and therapeutic targets. In this study, we firstly conducted analysis of global lncRNA expression patterns by using our own cohort (GSE73397) and two public available gene expression datasets: The Cancer Genome Atlas (TCGA) and GSE55909. Next, we performed microarray to observe genome-wide lncRNAs' expressions under dihydrotestosterone (DHT) stimulation in LNCaP cells (GSE72866), and overlapped the result with ChIPBase data to predict androgen-responsive lncRNAs with ARE...
August 19, 2016: Oncotarget
Bin Xu, Tao Tao, Yiduo Wang, Fang Fang, Yeqing Huang, Shuqiu Chen, Weidong Zhu, Ming Chen
Prostate cancer is one of the leading causes of death in men worldwide. Differentially expressed microRNAs (miRNAs) are associated with metastatic prostate cancer. However, their potential roles for affecting prostate cancer initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs in human metastatic prostate cancer tissues. We further validated our miRNA expression data using two large, independent clinical prostate cancer datasets from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA)...
August 14, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ana Cheong, Xiang Zhang, Yuk-Yin Cheung, Wan-Yee Tang, Jing Chen, Shu-Hua Ye, Mario Medvedovic, Yuet-Kin Leung, Gail S Prins, Shuk-Mei Ho
Developmental exposure to endocrine-disrupting chemicals (EDCs), 17β-estradiol-3-benzoate (EB) and bisphenol A (BPA), increases susceptibility to prostate cancer (PCa) in rodent models. Here, we used the methylated-CpG island recovery assay (MIRA)-assisted genomic tiling and CpG island arrays to identify treatment-associated methylome changes in the postnatal day (PND)90 dorsal prostate tissues of Sprague-Dawley rats neonatally (PND1, 3, and 5) treated with 25 µg/pup or 2,500 µg EB/kg body weight (BW) or 0...
July 14, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Daniel E Spratt, Tiffany Chan, Levi Waldron, Corey Speers, Felix Y Feng, Olorunseun O Ogunwobi, Joseph R Osborne
IMPORTANCE: Although poorly understood, there is heterogeneity in the molecular biology of cancer across race and ethnicities. The representation of racial minorities in large genomic sequencing efforts is unclear, and could have an impact on health care disparities. OBJECTIVE: To determine the racial distribution among samples sequenced within The Cancer Genome Atlas (TCGA) and the deficit of samples needed to detect moderately common mutational frequencies in racial minorities...
August 1, 2016: JAMA Oncology
Peter Ulz, Jelena Belic, Ricarda Graf, Martina Auer, Ingrid Lafer, Katja Fischereder, Gerald Webersinke, Karl Pummer, Herbert Augustin, Martin Pichler, Gerald Hoefler, Thomas Bauernhofer, Jochen B Geigl, Ellen Heitzer, Michael R Speicher
Genomic alterations in metastatic prostate cancer remain incompletely characterized. Here we analyse 493 prostate cancer cases from the TCGA database and perform whole-genome plasma sequencing on 95 plasma samples derived from 43 patients with metastatic prostate cancer. From these samples, we identify established driver aberrations in a cancer-related gene in nearly all cases (97.7%), including driver gene fusions (TMPRSS2:ERG), driver focal deletions (PTEN, RYBP and SHQ1) and driver amplifications (AR and MYC)...
2016: Nature Communications
Fujun Qin, Zhenguo Song, Maxwell Chang, Yansu Song, Henry Frierson, Hui Li
Neighboring genes transcribing in the same direction can form chimeric RNAs via cis-splicing (cis-SAGe). Previously, we reported 16 novel cis-SAGe chimeras in prostate cancer cell lines, and performed in silico validation on 14 pairs of normal and tumor samples from Chinese patients. However, whether these fusions exist in different populations, as well as their clinical implications, remains unclear. To investigate, we developed a bioinformatics pipeline using modified Spliced Transcripts Alignment to a Reference (STAR) to quantify these fusion RNAs simultaneously in silico...
September 28, 2016: Cancer Letters
Limin Zhang, Haowen Jiang, Gang Xu, Nan Chu, Ningxing Xu, Hui Wen, Bin Gu, Jun Liu, Shanghua Mao, Rong Na, Yan Jing, Qiang Ding, Yuanfang Zhang, Ling Wang
Early detection is the key to improve the prognosis of kidney cancer. This study profiled and identified differentially expressed serum proteins in stage T1a renal cell carcinoma (RCC) using isobaric tags for relative and absolute quantification (iTRAQ)-based mass spectrometry. A total amount of 99 serum samples including 29 patients with ccRCC, 24 patients with a benign kidney mass, 28 patients with another type of urological tumor (20 cases of transitional cell carcinoma and 8 cases of prostate cancer or a male genital tumor), and 18 healthy controls were subjected to iTRAQ-based mass spectrometry...
July 19, 2016: Bioscience Trends
Georgina Cosma, Giovanni Acampora, David Brown, Robert C Rees, Masood Khan, A Graham Pockley
The prediction of cancer staging in prostate cancer is a process for estimating the likelihood that the cancer has spread before treatment is given to the patient. Although important for determining the most suitable treatment and optimal management strategy for patients, staging continues to present significant challenges to clinicians. Clinical test results such as the pre-treatment Prostate-Specific Antigen (PSA) level, the biopsy most common tumor pattern (Primary Gleason pattern) and the second most common tumor pattern (Secondary Gleason pattern) in tissue biopsies, and the clinical T stage can be used by clinicians to predict the pathological stage of cancer...
2016: PloS One
Kazuya Shinmura, Hisami Kato, Yuichi Kawanishi, Kimio Yoshimura, Hisaki Igarashi, Masanori Goto, Hong Tao, Yusuke Inoue, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Haruhiko Sugimura
8-Hydroxyguanine (8OHG), a major oxidative DNA lesion, is known to accumulate in prostate cancer; however, the status of one of its repair enzymes, MUTYH, in prostate cancer remains to be elucidated. In this study, we showed that the expression levels of MUTYH mRNA and protein were significantly lower in prostate cancer than in non-cancerous prostatic tissue by examining two independent, publicly available databases and by performing an immunohistochemical analysis of prostate cancer specimens obtained at our hospital, respectively...
June 2, 2016: Molecular Carcinogenesis
M Khalid Khan Niazi, Keluo Yao, Debra Zynger, Steven Clinton, James Chen, Mehmet Koyuturk, Thomas LaFramboise, Metin Gurcan
Histopathologic features, particularly Gleason grading system, have contributed significantly to the diagnosis, treatment, and prognosis of prostate cancer for decades. However, prostate cancer demonstrates enormous heterogeneity in biological behavior, thus establishing improved prognostic and predictive markers is particularly important to personalize therapy of men with clinically localized and newly diagnosed malignancy. Many automated grading systems have been developed for Gleason grading but acceptance in the medical community has been lacking due to poor interpretability...
May 10, 2016: IEEE Journal of Biomedical and Health Informatics
H Zhao, Z Lu, F Bauzon, H Fu, J Cui, J Locker, L Zhu
SCF(Skp2/Cks1) ubiquitinates Thr187-phosphorylated p27 for degradation. Overexpression of Skp2 coupled with underexpression of p27 are frequent characteristics of cancer cells. When the role of SCF(Skp2/Cks1)-mediated p27 ubiquitination in cancer was specifically tested by p27 Thr187-to-Ala knockin (p27T187A KI), it was found dispensable for Kras(G12D)-induced lung tumorigenesis but essential for Rb1-deficient pituitary tumorigenesis. Here we identify pRb and p53 doubly deficient (DKO) prostate tumorigenesis as a context in which p27 ubiquitination by SCF(Skp2/Cks1) is required for p27 downregulation...
May 16, 2016: Oncogene
Ryan Stuchbery, Geoff Macintyre, Marek Cmero, Laurence M Harewood, Justin S Peters, Anthony J Costello, Christopher M Hovens, Niall M Corcoran
BACKGROUND: Despite the importance of androgen receptor (AR) signalling to prostate cancer development, little is known about how this signalling pathway changes with increasing grade and stage of the disease. OBJECTIVE: To explore changes in the normal AR transcriptome in localised prostate cancer, and its relation to adverse pathological features and disease recurrence. DESIGN: Publically accessible human prostate cancer expression arrays as well as RNA sequencing data from the prostate TCGA...
May 24, 2016: Oncotarget
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