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https://www.readbyqxmd.com/read/28216563/the-genomic-impact-of-dna-cpg-methylation-on-gene-expression-relationships-in-prostate-cancer
#1
REVIEW
Mark D Long, Dominic J Smiraglia, Moray J Campbell
The process of DNA CpG methylation has been extensively investigated for over 50 years and revealed associations between changing methylation status of CpG islands and gene expression. As a result, DNA CpG methylation is implicated in the control of gene expression in developmental and homeostasis processes, as well as being a cancer-driver mechanism. The development of genome-wide technologies and sophisticated statistical analytical approaches has ushered in an era of widespread analyses, for example in the cancer arena, of the relationships between altered DNA CpG methylation, gene expression, and tumor status...
February 14, 2017: Biomolecules
https://www.readbyqxmd.com/read/28213802/high-expression-of-aspm-correlates-with-tumor-progression-and-predicts-poor-outcome-in-patients-with-prostate-cancer
#2
Jian-Jiang Xie, Yang-Jia Zhuo, Yu Zheng, Ru-Jun Mo, Ze-Zhen Liu, Bo-Wei Li, Zhi-Duan Cai, Xue-Jin Zhu, Yu-Xiang Liang, Hui-Chan He, Wei-de Zhong
PURPOSE: Abnormal spindle microtubule assembly (ASPM) gene was known to be linked with poor clinical prognosis in various tumors. However, the clinical significance of ASPM in prostate cancer (PCa) has not yet been understood. The purpose of this study was to determine the association of ASPM with tumor progression and prognosis in PCa patients. METHODS: The expression of ASPM at protein level in human PCa and non-cancerous prostate tissue was detected by immunohistochemical analysis, which was further validated by using microarray-based dataset (NCBI GEO: GSE21032 and The Cancer Genome Atlas (TCGA) dataset) at mRNA level...
February 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28138401/t-cadherin-in-prostate-cancer-relationship-with-cancer-progression-differentiation-and-drug-resistance
#3
Boris Dasen, Tatjana Vlajnic, Chantal Mengus, Christian Ruiz, Lukas Bubendorf, Giulio Spagnoli, Stephen Wyler, Paul Erne, Thérèse J Resink, Maria Philippova
Prostate cancer represents the second leading cause of cancer-related death in men. T-cadherin (CDH13) is an atypical GPI-anchored member of the cadherin family of adhesion molecules. Its gene was reported to be downregulated in a small series of prostate tumours. T-cadherin protein expression/localisation in prostate tissue has never been investigated. The purpose of our study was to analyse CDH13 gene and protein levels in large sets of healthy and cancer prostate tissue specimens and evaluate CDH13 effects on the sensitivity of prostate cancer cells to chemotherapy...
January 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28125091/microrna-466-inhibits-tumor-growth-and-bone-metastasis-in-prostate-cancer-by-direct-regulation-of-osteogenic-transcription-factor-runx2
#4
Melissa Colden, Altaf A Dar, Sharanjot Saini, Priya V Dahiya, Varahram Shahryari, Soichiro Yamamura, Yuichiro Tanaka, Gary Stein, Rajvir Dahiya, Shahana Majid
MicroRNAs (miRNAs) have emerged as key players in cancer progression and metastatic initiation yet their importance in regulating prostate cancer (PCa) metastasis to bone has begun to be appreciated. We employed multimodal strategy based on in-house PCa clinical samples, publicly available TCGA cohorts, a panel of cell lines, in silico analyses, and a series of in vitro and in vivo assays to investigate the role of miR-466 in PCa. Expression analyses revealed that miR-466 is under-expressed in PCa compared to normal tissues...
January 26, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28113734/visually-meaningful-histopathological-features-for-automatic-grading-of-prostate-cancer
#5
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
https://www.readbyqxmd.com/read/28107606/dishevelled-segment-polarity-protein-3-dvl3-a-novel-and-easily-applicable-recurrence-predictor-in-localized-prostate-adenocarcinoma
#6
Pil-Jong Kim, Ji Y Park, Hong-Gee Kim, Yong Mee Cho, Heounjeong Go
OBJECTIVE: To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. PATIENTS AND METHODS: Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28105922/differential-expression-of-alternatively-spliced-transcripts-related-to-energy-metabolism-in-colorectal-cancer
#7
Anastasiya Vladimirovna Snezhkina, George Sergeevich Krasnov, Andrew Rostislavovich Zaretsky, Alex Zhavoronkov, Kirill Mikhailovich Nyushko, Alexey Alexandrovich Moskalev, Irina Yurievna Karpova, Anastasiya Isaevna Afremova, Anastasiya Valerievna Lipatova, Dmitriy Vladimitovich Kochetkov, Maria Sergeena Fedorova, Nadezhda Nikolaevna Volchenko, Asiya Fayazovna Sadritdinova, Nataliya Vladimirovna Melnikova, Dmitry Vladimirovich Sidorov, Anatoly Yurievich Popov, Dmitry Valerievich Kalinin, Andrey Dmitrievich Kaprin, Boris Yakovlevich Alekseev, Alexey Alexandrovich Dmitriev, Anna Viktorovna Kudryavtseva
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC...
December 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/28069585/expression-of-hmgb2-indicates-worse-survival-of-patients-and-is-required-for-the-maintenance-of-warburg-effect-in-pancreatic-cancer
#8
Xin Cai, Hongjian Ding, Yanxia Liu, Gaofeng Pan, Qingguo Li, Zhen Yang, Weiyan Liu
High mobility group proteins (HMGs) are the second most abundant chromatin proteins and exert global genomic functions in the establishment of active or inactive chromatin domains. Through interaction with nucleosomes, transcription factors, nucleosome-remodeling machines and histones, the HMGs family proteins contribute to the fine tuning of transcription in response to rapid environmental changes. Mammalian high mobility group Bs (HMGBs) are characterized by two tandem HMG box domains followed by a long acidic tail...
January 9, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28012134/elevated-levels-of-epithelial-cell-transforming-sequence-2-predicts-poor-prognosis-for-prostate-cancer
#9
Zhenghui Guo, Xianju Chen, Tao Du, Dingjun Zhu, Yiming Lai, Wen Dong, Wanhua Wu, Chunhao Lin, Leyuan Liu, Hai Huang
Epithelial cell transforming sequence 2 (Ect2) was originally reported as an oncogene that is involved in several types of human cancers. However, little is known about its expression and function in prostate cancer. Immunohistochemical staining for Ect2 was performed on a human tissue microarray. The staining intensity was analyzed in association with clinical pathological parameters such as Gleason score, pathological grade, clinical stage, tumor invasion, lymph node and distant metastasis. Furthermore, we repeated such analysis and investigated the prognostic value of Ect2 using the TCGA (The Cancer Genome Atlas) Dataset...
January 2017: Medical Oncology
https://www.readbyqxmd.com/read/27853645/promoter-methylation-of-the-immune-checkpoint-receptor-pd-1-pdcd1-is-an-independent-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients-following-radical-prostatectomy
#10
Diane Goltz, Heidrun Gevensleben, Jörn Dietrich, Jörg Ellinger, Jennifer Landsberg, Glen Kristiansen, Dimo Dietrich
Biomarkers that facilitate the prediction of disease recurrence in prostate cancer (PCa) may enable physicians to personalize treatment for individual patients. In the current study, PD-1 (PDCD1) promoter methylation was assessed in a cohort of 498 PCa patients included in The Cancer Genome Atlas (TCGA) and a second cohort of 300 PCa cases treated at the University Hospital of Bonn. In the TCGA cohort, the PD-1 promoter was significantly hypermethylated in carcinomas versus normal prostatic epithelium (55.5% vs...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27832783/mir-375-induces-docetaxel-resistance-in-prostate-cancer-by-targeting-sec23a-and-yap1
#11
Yuan Wang, Rachel Lieberman, Jing Pan, Qi Zhang, Meijun Du, Peng Zhang, Marja Nevalainen, Manish Kohli, Niraj K Shenoy, Hui Meng, Ming You, Liang Wang
BACKGROUND: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically are centered on docetaxel-based chemotherapy. We previously reported that elevated miR-375 levels were significantly associated with poor overall survival of mCRPC patients. In this study, we evaluated if miR-375 induced chemo-resistance to docetaxel through regulating target genes associated with drug resistance. METHODS: We first compared miR-375 expression level between prostate cancer tissues and normal prostate tissues using data from The Cancer Genome Atlas (TCGA)...
November 10, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27819678/tet2-binds-the-androgen-receptor-and-loss-is-associated-with-prostate-cancer
#12
M L Nickerson, S Das, K M Im, S Turan, S I Berndt, H Li, H Lou, S A Brodie, J N Billaud, T Zhang, A J Bouk, D Butcher, Z Wang, L Sun, K Misner, W Tan, A Esnakula, D Esposito, W Y Huang, R N Hoover, M A Tucker, J R Keller, J Boland, K Brown, S K Anderson, L E Moore, W B Isaacs, S J Chanock, M Yeager, M Dean, T Andresson
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumours in the methylcytosine dioxygenase ten-eleven translocation 2 (TET2), which is altered in 5-15% of myeloid, kidney, colon and PCas. Genome-wide association studies previously identified non-coding risk variants associated with PCa and melanoma. We perform fine-mapping of PCa risk across TET2 using genotypes from the PEGASUS case-control cohort and identify six new risk variants in introns 1 and 2...
November 7, 2016: Oncogene
https://www.readbyqxmd.com/read/27807836/computational-methods-and-correlation-of-exon-skipping-events-with-splicing-transcription-and-epigenetic-factors
#13
Jianbo Wang, Zhenqing Ye, Tim H Huang, Huidong Shi, Victor X Jin
Alternative splicing is widely recognized for playing roles in regulating genes and creating gene diversity. Consequently the identification and quantification of differentially spliced transcripts are pivotal for transcriptome analysis. However, how these diversified isoforms are spliced during genomic transcription and protein expression and what biological factors might influence the regulation of this are still required for further exploration. The advances in next-generation sequencing of messenger RNA (RNA-seq) have enabled us to survey gene expression and splicing more accurately...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27723507/improving-information-retrieval-in-functional-analysis
#14
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
https://www.readbyqxmd.com/read/27708722/pitx3-promoter-methylation-is-a-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients-after-radical-prostatectomy
#15
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
https://www.readbyqxmd.com/read/27695045/tumor-specific-epigenetic-silencing-of-corticotropin-releasing-hormone-binding-protein-in-renal-cell-carcinoma-association-of-hypermethylation-and-metastasis
#16
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
https://www.readbyqxmd.com/read/27689475/cdo1-promoter-methylation-is-associated-with-gene-silencing-and-is-a-prognostic-biomarker-for-biochemical-recurrence-free-survival-in-prostate-cancer-patients
#17
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...
December 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27678455/pan-cancer-analysis-of-the-mediator-complex-transcriptome-identifies-cdk19-and-cdk8-as-therapeutic-targets-in-advanced-prostate-cancer
#18
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
https://www.readbyqxmd.com/read/27651837/epigenetic-signature-of-gleason-score-and-prostate-cancer-recurrence-after-radical-prostatectomy
#19
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
https://www.readbyqxmd.com/read/27623992/epigenetic-loss-of-putative-tumor-suppressor-sfrp3-correlates-with-poor-prognosis-of-lung-adenocarcinoma-patients
#20
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
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