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https://www.readbyqxmd.com/read/28643332/integrative-eqtl-analysis-of-tumor-and-host-omics-data-in-individuals-with-bladder-cancer
#1
Silvia Pineda, Kristel Van Steen, Núria Malats
Integrative analyses of several omics data are emerging. The data are usually generated from the same source material (i.e., tumor sample) representing one level of regulation. However, integrating different regulatory levels (i.e., blood) with those from tumor may also reveal important knowledge about the human genetic architecture. To model this multilevel structure, an integrative-expression quantitative trait loci (eQTL) analysis applying two-stage regression (2SR) was proposed. This approach first regressed tumor gene expression levels with tumor markers and the adjusted residuals from the previous model were then regressed with the germline genotypes measured in blood...
June 23, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/28605401/comparison-of-pre-processing-methods-for-infinium-humanmethylation450-beadchip-array
#2
Yu-Jia Shiah, Michael Fraser, Robert G Bristow, Paul C Boutros
Motivation: Microarrays are widely used to quantify DNA methylation because they are economical, require only small quantities of input DNA and focus on well-characterized regions of the genome. However, pre-processing of methylation microarray data is challenging because of confounding factors that include background fluorescence, dye bias and the impact of germline polymorphisms. Therefore, we present valuable insights and a framework for those seeking the most optimal pre-processing method through a data-driven approach...
June 10, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28581528/dna-methylation-variations-are-required-for-epithelial-to-mesenchymal-transition-induced-by-cancer-associated-fibroblasts-in-prostate-cancer-cells
#3
C Pistore, E Giannoni, T Colangelo, F Rizzo, E Magnani, L Muccillo, G Giurato, M Mancini, S Rizzo, M Riccardi, N Sahnane, V Del Vescovo, K Kishore, M Mandruzzato, F Macchi, M Pelizzola, M A Denti, D Furlan, A Weisz, V Colantuoni, P Chiarugi, I M Bonapace
Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting our consolidated 'ex-vivo' system, we show that cancer-associated fibroblasts (CAFs) released factors have pivotal roles in inducing genome methylation changes required for EMT and stemness in EMT-prone PCa cells...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28558729/high-throughput-validation-of-cerna-regulatory-networks
#4
Hua-Sheng Chiu, María Rodríguez Martínez, Mukesh Bansal, Aravind Subramanian, Todd R Golub, Xuerui Yang, Pavel Sumazin, Andrea Califano
BACKGROUND: MicroRNAs (miRNAs) play multiple roles in tumor biology. Interestingly, reports from multiple groups suggest that miRNA targets may be coupled through competitive stoichiometric sequestration. Specifically, computational models predicted and experimental assays confirmed that miRNA activity is dependent on miRNA target abundance, and consequently, changes in the abundance of some miRNA targets lead to changes to the regulation and abundance of their other targets. The resulting indirect regulatory influence between miRNA targets resembles competition and has been dubbed competitive endogenous RNA (ceRNA)...
May 30, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28511652/ing3-promotes-prostate-cancer-growth-by-activating-the-androgen-receptor
#5
Arash Nabbi, Urszula L McClurg, Subhash Thalappilly, Amal Almami, Mahsa Mobahat, Tarek A Bismar, Olivier Binda, Karl T Riabowol
BACKGROUND: The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development...
May 16, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28496006/gene-expression-signature-of-gleason-score-is-associated-with-prostate-cancer-outcomes-in-a-radical-prostatectomy-cohort
#6
Min A Jhun, Milan S Geybels, Jonathan L Wright, Suzanne Kolb, Craig April, Marina Bibikova, Elaine A Ostrander, Jian-Bing Fan, Ziding Feng, Janet L Stanford
Prostate cancer (PCa) is a leading cause of cancer-related mortality worldwide. Gleason score (GS) is one of the best predictors of PCa aggressiveness, but additional tumor biomarkers may improve its prognostic accuracy. We developed a gene expression signature of GS to enhance the prediction of PCa outcomes. Elastic net was used to construct a gene expression signature by contrasting GS 8-10 vs. ≤6 tumors in The Cancer Genome Atlas (TCGA) dataset. The constructed signature was then evaluated for its ability to predict recurrence and metastatic-lethal (ML) progression in a Fred Hutchinson (FH) patient cohort (N=408; NRecurrence=109; NMLprogression=27)...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427506/recent-advances-in-genitourinary-tumors-a-review-focused-on-biology-and-systemic-treatment
#7
REVIEW
Aránzazu González Del Alba, José Ángel Arranz, Javier Puente, María José Méndez-Vidal, Enrique Gallardo, Enrique Grande, Begoña Pérez-Valderrama, Enrique González-Billalabeitia, Martín Lázaro-Quintela, Álvaro Pinto, Nuria Lainez, Josep M Piulats, Emilio Esteban, José Pablo Maroto Rey, Jorge A García, Cristina Suárez
Updated information published up to 2016 regarding major advances in renal cancer, bladder cancer, and prostate cancer is here presented. Based on an ever better understanding of the genetic and molecular alterations that govern the initial pathogenic mechanisms of tumor oncogenesis, an improvement in the characterization and treatment of urologic tumors has been achieved in the past year. According to the Cancer Genome Atlas (ATLAS) project, alterations in the MET pathway are characteristics of type 1 papillary renal cell carcinomas, and activation of NRF2-ARE pathway is associated with the biologically distinct type 2...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28416734/the-angiotensin-receptor-blocker-losartan-inhibits-mammary-tumor-development-and-progression-to-invasive-carcinoma
#8
Rhiannon Coulson, Seng H Liew, Angela A Connelly, Nicholas S Yee, Siddhartha Deb, Beena Kumar, Ana C Vargas, Sandra A O'Toole, Adam C Parslow, Ashleigh Poh, Tracy Putoczki, Riley J Morrow, Mariah Alorro, Kyren A Lazarus, Evie F W Yeap, Kelly L Walton, Craig A Harrison, Natalie J Hannan, Amee J George, Colin D Clyne, Matthias Ernst, Andrew M Allen, Ashwini L Chand
Drugs that target the Renin-Angiotensin System (RAS) have recently come into focus for their potential utility as cancer treatments. The use of Angiotensin Receptor Blockers (ARBs) and Angiotensin-Converting Enzyme (ACE) Inhibitors (ACEIs) to manage hypertension in cancer patients is correlated with improved survival outcomes for renal, prostate, breast and small cell lung cancer. Previous studies demonstrate that the Angiotensin Receptor Type I (AT1R) is linked to breast cancer pathogenesis, with unbiased analysis of gene-expression studies identifying significant up-regulation of AGTR1, the gene encoding AT1R in ER+ve/HER2-ve tumors correlating with poor prognosis...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415613/promoter-dna-methylation-analysis-reveals-a-combined-diagnosis-of-cpg-based-biomarker-for-prostate-cancer
#9
Yuanyuan Tang, Shusuan Jiang, Yinmin Gu, Weidong Li, Zengnan Mo, Yuanjie Huang, Tianyu Li, Yanling Hu
BACKGROUND: Prostate cancer (PCa) is the most common tumor in elderly men. However, the specificity and sensitivity of serum prostate-specific antigen levels in PCa diagnosis are controversial. This study aims to reveal a novel diagnosis biomarker in PCa. MATERIALS AND METHODS: The differential methylated CpG sites between 423 primary PCa and 39 adjacent samples from The Cancer Genome Atlas (TCGA) on Illumina HumanMethylation 450 platform were analyzed. The diagnostic methylation markers were mined using the Prediction Analysis of Microarrays package in Bioconductor...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28389666/molecular-classification-of-prostate-adenocarcinoma-by-the-integrated-somatic-mutation-profiles-and-molecular-network
#10
Lei Yang, Shiyuan Wang, Meng Zhou, Xiaowen Chen, Wei Jiang, Yongchun Zuo, Yingli Lv
Prostate cancer is one of the most common cancers in men and a leading cause of cancer death worldwide, displaying a broad range of heterogeneity in terms of clinical and molecular behavior. Increasing evidence suggests that classifying prostate cancers into distinct molecular subtypes is critical to exploring the potential molecular variation underlying this heterogeneity and to better treat this cancer. In this study, the somatic mutation profiles of prostate cancer were downloaded from the TCGA database and used as the source nodes of the random walk with restart algorithm (RWRA) for generating smoothed mutation profiles in the STRING network...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28361034/combinatorial-ranking-of-gene-sets-to-predict-disease-relapse-the-retinoic-acid-pathway-in-early-prostate-cancer
#11
Hieu T Nim, Milena B Furtado, Mirana Ramialison, Sarah E Boyd
BACKGROUND: Quantitative high-throughput data deposited in consortia such as International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) present opportunities and challenges for computational analyses. METHODS: We present a computational strategy to systematically rank and investigate a large number (2(10)-2(20)) of clinically testable gene sets, using combinatorial gene subset generation and disease-free survival (DFS) analyses. This approach integrates protein-protein interaction networks, gene expression, DNA methylation, and copy number data, in association with DFS profiles from patient clinical records...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28342983/lipid-quantification-by-raman-microspectroscopy-as-a-potential-biomarker-in-prostate-cancer
#12
Jordan O'Malley, Rahul Kumar, Andrey N Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
July 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28258894/pan-cancer-analysis-of-genomic-sequencing-among-the-elderly
#13
Daniel R Wahl, Paul L Nguyen, Maria Santiago, Kasra Yousefi, Elai Davicioni, Dean A Shumway, Corey Speers, Rohit Mehra, Felix Y Feng, Joseph R Osborne, Daniel E Spratt
PURPOSE: We hypothesized that elderly patients might have age-specific genetic abnormalities yet be underrepresented in currently available sequencing repositories, which could limit the effect of sequencing efforts for this population. METHODS AND MATERIALS: Leveraging The Cancer Genome Atlas (TCGA) data portal, 9 tumor types were analyzed. The frequency distribution of cancer by age was determined and compared with Surveillance, Epidemiology, and End Results data...
January 7, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28216563/the-genomic-impact-of-dna-cpg-methylation-on-gene-expression-relationships-in-prostate-cancer
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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