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https://www.readbyqxmd.com/read/29029484/ybx1-promotes-tumor-growth-by-elevating-glycolysis-in-human-bladder-cancer
#1
Liuyu Xu, Hongyun Li, Longchao Wu, Shiming Huang
Aerobic glycolysis, also known as Warburg effect, is a key hallmark of cancers. The Y-box-binding protein 1 (YBX1) is a well-known oncoprotein implicated in multiple malignant phenotypes of cancers. Meanwhile, little is known about the oncogenic functions and mechanisms of YBX1 in bladder cancer. Based on gene set enrichment analysis (GSEA) of TCGA RNAseq data, we find that YBX1 was profoundly involved in the glycolysis part of glucose metabolism. Loss- and gain-of-function studies show that YBX1 can enhance glycolysis as revealed by expression of glycolytic enzymes, glucose uptake, lactate secretion and extracellular acidification rate (ECAR)...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28988769/comprehensive-molecular-characterization-of-muscle-invasive-bladder-cancer
#2
A Gordon Robertson, Jaegil Kim, Hikmat Al-Ahmadie, Joaquim Bellmunt, Guangwu Guo, Andrew D Cherniack, Toshinori Hinoue, Peter W Laird, Katherine A Hoadley, Rehan Akbani, Mauro A A Castro, Ewan A Gibb, Rupa S Kanchi, Dmitry A Gordenin, Sachet A Shukla, Francisco Sanchez-Vega, Donna E Hansel, Bogdan A Czerniak, Victor E Reuter, Xiaoping Su, Benilton de Sa Carvalho, Vinicius S Chagas, Karen L Mungall, Sara Sadeghi, Chandra Sekhar Pedamallu, Yiling Lu, Leszek J Klimczak, Jiexin Zhang, Caleb Choo, Akinyemi I Ojesina, Susan Bullman, Kristen M Leraas, Tara M Lichtenberg, Catherine J Wu, Nicholaus Schultz, Gad Getz, Matthew Meyerson, Gordon B Mills, David J McConkey, John N Weinstein, David J Kwiatkowski, Seth P Lerner
We report a comprehensive analysis of 412 muscle-invasive bladder cancers characterized by multiple TCGA analytical platforms. Fifty-eight genes were significantly mutated, and the overall mutational load was associated with APOBEC-signature mutagenesis. Clustering by mutation signature identified a high-mutation subset with 75% 5-year survival. mRNA expression clustering refined prior clustering analyses and identified a poor-survival "neuronal" subtype in which the majority of tumors lacked small cell or neuroendocrine histology...
October 4, 2017: Cell
https://www.readbyqxmd.com/read/28977887/risk-score-based-on-three-mrna-expression-predicts-the-survival-of-bladder-cancer
#3
Qingzuo Liu, Ruigang Diao, Guoyan Feng, Xiaodong Mu, Aiqun Li
Bladder cancer (BLCA) is one of the most malignant cancers worldwide, and its prognosis varies. 1214 BLCA samples in five different datasets and 2 platforms were enrolled in this study. By utilizing the gene expression in The Cancer Genome Atlas (TCGA) dataset, and another two datasets, in GSE13507 and GSE31684, we constructed a risk score staging system with Cox multivariate regression to evaluate predict the outcome of BLCA patients. Three genes consist of RCOR1, ST3GAL5, and COL10A1 were used to predict the survival of BLCA patients...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977858/identification-of-hmex-3a-and-its-effect-on-human-bladder-cancer-cell-proliferation
#4
Ying Huang, Chao Fang, Jing-Wen Shi, Yu Wen, Da Liu
In this study, hMex-3A was selected from TCGA database as a research object to observe the effects of small interfering RNA (siRNA) targeting hMex-3A on the biological activities of human bladder cancer and explore its mechanism for the first time. In this study, there were 2 groups including negative control group and hMex-3A-siRNA-transfected cells group for 5637 and T24 cell lines, respectively. After bladder cancer cells were transfected with the interference RNA sequence, proliferation of transfected cells were assessed by Celigo Cell Counting, and apoptosis were detected by flow cytometry...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28972965/hyaluronic-acid-family-in-bladder-cancer-potential-prognostic-biomarkers-and-therapeutic-targets
#5
Daley S Morera, Martin S Hennig, Asif Talukder, Soum D Lokeshwar, Jiaojiao Wang, Michael Garcia-Roig, Nicolas Ortiz, Travis J Yates, Luis E Lopez, Georgios Kallifatidis, Mario W Kramer, Andre R Jordan, Axel S Merseburger, Murugesan Manoharan, Mark S Soloway, Martha K Terris, Vinata B Lokeshwar
BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models...
October 3, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28912897/genomic-analysis-of-tumor-microenvironment-immune-types-across-14-solid-cancer-types-immunotherapeutic-implications
#6
Yu-Pei Chen, Yu Zhang, Jia-Wei Lv, Ying-Qin Li, Ya-Qin Wang, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Yan-Ping Mao, Jing-Ping Yun, Na Liu, Jun Ma
We performed a comprehensive immuno-genomic analysis of tumor microenvironment immune types (TMITs), which is classified into four groups based on PD-L1+CD8A or PD-L1+cytolytic activity (CYT) expression, across a broad spectrum of solid tumors in order to help identify patients who will benefit from anti- PD-1/PD-L1 therapy. The mRNA sequencing data from The Cancer Genome Atlas (TCGA) of 14 solid cancer types representing 6,685 tumor samples was analyzed. TMIT was classified only for those tumor types that both PD-L1 and CD8A/CYT could prefict mutation and/or neoantigen number...
2017: Theranostics
https://www.readbyqxmd.com/read/28894827/the-genetic-landscape-of-programmed-death-ligand-1-pd-l1-alterations-in-head-and-neck-cancer
#7
Thomas E Heineman, Adam Widman, Edward C Kuan, Maie St John
OBJECTIVES: Nivolumab has recently been shown in the phase III clinical trial CheckMate-141 to have superior survival rates compared to the current standard of care chemotherapy for recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC). Nivolumab targets the immune inhibitory receptor programmed cell death 1 (PD-1). Programmed cell death ligand 1 (PD-L1) genomics have been poorly characterized in the context of HNSCC, including expression levels of PD-L1 in individual tumors as well as related up or down-regulated genes that might function as co-targets...
June 2017: Laryngoscope Investigative Otolaryngology
https://www.readbyqxmd.com/read/28765327/the-kmt1a-gata3-stat3-circuit-is-a-novel-self-renewal-signaling-of-human-bladder-cancer-stem-cells
#8
Tingyi Wen, Zhao Yang, Luyun He, Kaisu Lin, Yun Zhang, Aihua Deng, Yong Liang, Chong Li
Bladder cancer (BC) is one of the most common urinary malignancies worldwide characterized by a high rate of recurrence and no targeted therapy method. Bladder cancer stem cells (BCSCs) play a crucial role in tumor initiation, metastasis and drug-resistance. However, the regulatory signaling and self-renewal mechanisms of BCSCs remain largely unknown. Here, we identified a novel signal, the KMT1A-GATA3-STAT3 circuit, which promoted the self-renewal and tumorigenicity of human BCSCs.<br />Experimental Design: In a discovery step, human BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary BC samples #1 and #2, and the BC cell line EJ were analyzed by transcriptome microarray...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28753846/the-landscape-of-whole-genome-alterations-and-pathologic-features-in-genitourinary-malignancies-an-analysis-of-the-cancer-genome-atlas
#9
Mark W Ball, Michael A Gorin, Charles G Drake, Hans J Hammers, Mohamad E Allaf
BACKGROUND: The accumulation of somatic genetic alterations drives carcinogenesis. Little is known, however, about how the level of genetic alteration across an entire cancer genome affects tumor grade, stage or survival. OBJECTIVE: To investigate the influence of somatic mutation count (MC) and copy number variation (CNV) on pathologic and oncologic outcomes in patients with genitourinary malignancies in The Cancer Genome Atlas (TCGA). DESIGN, SETTING, AND PARTICIPANTS: TCGA data sets for adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA), chromophobe renal cell carcinoma (RCC; KICH), clear cell RCC (KIRC), papillary RCC (KIRP), pheochromocytoma and paraganglioma (PCPG), prostate adenocarcinoma (PRAD), and testis germ cell tumor (TGCT) were accessed via cBioportal...
February 8, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28752236/opa-interacting-protein-5-acts-as-an-oncogene-in-bladder-cancer
#10
Xuefeng He, Jianquan Hou, Jigen Ping, Duangai Wen, Jun He
PURPOSE: To explore the biological functions and mechanism of Opa interacting protein 5 (OIP5) in bladder cancer (BC). METHODS: We investigated the expression of OIP5 in BC through immunohistochemical staining (IHC) and its correlation with clinicopathologic features of BC patients. Moreover, knockdown of OIP5 was performed in BC cell lines and colony formation capacity, cell growth curve, cell cycle phase and cell apoptosis assay was applied for investigating the roles of OIP5 in BC...
November 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28695825/tsc2-disruption-in-mesenchymal-progenitors-results-in-tumors-with-vascular-anomalies-overexpressing-lgals3
#11
Peter J Klover, Rajesh L Thangapazham, Jiro Kato, Ji-An Wang, Stasia A Anderson, Victoria Hoffmann, Wendy K Steagall, Shaowei Li, Elizabeth McCart, Neera Nathan, Joshua D Bernstock, Matthew D Wilkerson, Clifton L Dalgard, Joel Moss, Thomas N Darling
Increased mTORC1 signaling from TSC1/TSC2 inactivation is found in cancer and causes tuberous sclerosis complex (TSC). The role of mesenchymal-derived cells in TSC tumorigenesis was investigated through disruption of Tsc2 in craniofacial and limb bud mesenchymal progenitors. Tsc2cKO(Prrx1-cre) mice had shortened lifespans and extensive hamartomas containing abnormal tortuous, dilated vessels prominent in the forelimbs. Abnormalities were blocked by the mTORC1 inhibitor sirolimus. A Tsc2/mTORC1 expression signature identified in Tsc2-deficient fibroblasts was also increased in bladder cancers with TSC1/TSC2 mutations in the TCGA database...
July 11, 2017: ELife
https://www.readbyqxmd.com/read/28679867/risk-score-based-on-three-mrna-expression-predicts-the-survival-of-bladder-cancer
#12
Qingzuo Liu, Ruigang Diao, Guoyan Feng, Xiaodong Mu, Aiqun Li
Bladder cancer (BLCA) is one of the most malignant cancers worldwide, and its prognosis varies. 1214 BLCA samples in five different datasets and 2 platforms were enrolled in this study. By utilizing the gene expression in The Cancer Genome Atlas (TCGA) dataset, and another two datasets, in GSE13507 and GSE31684, we constructed a risk score staging system with Cox multivariate regression to evaluate predict the outcome of BLCA patients. Three genes consist of RCOR1, ST3GAL5, and COL10A1 were used to predict the survival of BLCA patients...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643332/integrative-eqtl-analysis-of-tumor-and-host-omics-data-in-individuals-with-bladder-cancer
#13
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/28600503/transcriptome-sequencing-identifies-anln-as-a-promising-prognostic-biomarker-in-bladder-urothelial-carcinoma
#14
Shuxiong Zeng, Xiaowen Yu, Chong Ma, Ruixiang Song, Zhensheng Zhang, Xiaoyuan Zi, Xin Chen, Yang Wang, Yongwei Yu, Junjie Zhao, Rongchao Wei, Yinghao Sun, Chuanliang Xu
The prognosis of bladder urothelial carcinoma (BLCA) varies greatly even for patients with similar pathological characteristics. We conducted transcriptome sequencing on ten pairs of BLCA samples and adjacent normal tissues to identify differentially expressed genes. Anillin (ANLN) was identified as a transcript that was significantly up-regulated in BLCA samples compared with normal tissues. Prognostic power of candidate gene was studied using qRT-PCR and immunohistochemistry on 40 and 209 patients, respectively...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591741/identification-of-hmex-3a-and-its-effect-on-human-bladder-cancer-cell-proliferation
#15
Ying Huang, Chao Fang, Jing-Wen Shi, Yu Wen, Da Liu
In this study, hMex-3A was selected from TCGA database as a research object to observe the effects of small interfering RNA (siRNA) targeting hMex-3A on the biological activities of human bladder cancer and explore its mechanism for the first time. In this study, there were 2 groups including negative control group and hMex-3A-siRNA-transfected cells group for 5637 and T24 cell lines, respectively. After bladder cancer cells were transfected with the interference RNA sequence, proliferation of transfected cells were assessed by Celigo Cell Counting, and apoptosis were detected by flow cytometry...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589857/identification-of-epigenetic-interactions-between-mirna-and-dna-methylation-associated-with-gene-expression-as-potential-prognostic-markers-in-bladder-cancer
#16
Manu Shivakumar, Younghee Lee, Lisa Bang, Tullika Garg, Kyung-Ah Sohn, Dokyoon Kim
BACKGROUND: One of the fundamental challenges in cancer is to detect the regulators of gene expression changes during cancer progression. Through transcriptional silencing of critical cancer-related genes, epigenetic change such as DNA methylation plays a crucial role in cancer. In addition, miRNA, another major component of epigenome, is also a regulator at the post-transcriptional levels that modulate transcriptome changes. However, a mechanistic role of synergistic interactions between DNA methylation and miRNA as epigenetic regulators on transcriptomic changes and its association with clinical outcomes such as survival have remained largely unexplored in cancer...
May 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28515962/analyses-of-publicly-available-genomics-resources-define-fgf-2-expressing-bladder-carcinomas-as-emt-prone-proliferative-tumors-with-low-mutation-rates-and-high-expression-of-ctla-4-pd-1-and-pd-l1
#17
Elizabeth A McNiel, Philip N Tsichlis
FGF-2 is overexpressed in a subset of invasive bladder carcinomas and its overexpression correlates with poor prognosis. Analyses of publicly available databases addressing the molecular mechanisms that may be responsible for the poor prognosis of these tumors, revealed that FGF-2 expression correlates positively with the expression of EMT-promoting transcription factors and with changes in gene expression that are characteristic of EMT. The same analyses also revealed that FGF-2 correlates negatively with the expression, mutation and copy number variations of FGFR-3, all of which are associated with non-invasive bladder carcinomas...
2017: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/28507806/preclinical-efficacy-of-immune-checkpoint-monotherapy-does-not-recapitulate-corresponding-biomarkers-based-clinical-predictions-in-glioblastoma
#18
Abhishek D Garg, Lien Vandenberk, Matthias Van Woensel, Jochen Belmans, Marco Schaaf, Louis Boon, Steven De Vleeschouwer, Patrizia Agostinis
Glioblastoma (GBM) is resistant to most multimodal therapies. Clinical success of immune-checkpoint inhibitors (ICIs) has spurred interest in applying ICIs targeting CTLA4, PD1 or IDO1 against GBM. This amplifies the need to ascertain GBM's intrinsic susceptibility (or resistance) toward these ICIs, through clinical biomarkers that may also "guide and prioritize" preclinical testing. Here, we interrogated the TCGA and/or REMBRANDT human patient-cohorts to predict GBM's predisposition toward ICIs. We exploited various broad clinical biomarkers, including mutational or predicted-neoantigen burden, pre-existing or basal levels of tumor-infiltrating T lymphocytes (TILs), differential expression of immune-checkpoints within the tumor and their correlation with particular TILs/Treg-associated functional signature and prognostic impact of differential immune-checkpoint expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28507798/tumor-infiltrating-neutrophils-predict-benefit-from-adjuvant-chemotherapy-in-patients-with-muscle-invasive-bladder-cancer
#19
Lin Zhou, Le Xu, Lingli Chen, Qiang Fu, Zheng Liu, Yuan Chang, Zongming Lin, Jiejie Xu
Growing evidence shows tumor-infiltrating neutrophils (TINs) involvement in tumorigenesis. The objective of this study is to assess the prognostic effect of TINs and its impact on adjuvant chemotherapy benefits in muscle invasive bladder cancer (MIBC). A total of 142 MIBC patients from Zhongshan Hospital, 119 MIBC patients from FUSCC, and 405 MIBC patients from TCGA cohort were enrolled in the study. TINs were evaluated by immunohistochemical staining of CD66b or the CIBERSORT method. Patients with high TINs had a significantly poorer overall survival (p = 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28466543/mutation-patterns-in-genes-encoding-interferon-signaling-and-antigen-presentation-a-pan-cancer-survey-with-implications-for-the-use-of-immune-checkpoint-inhibitors
#20
Jan Budczies, Michael Bockmayr, Frederick Klauschen, Volker Endris, Stefan Fröhling, Peter Schirmacher, Carsten Denkert, Albrecht Stenzinger
Blockade of immune checkpoints has become a powerful tool in cancer medicine, which is effective across various solid cancer types and hematologic malignancies. While immunohistochemical detection of PD-L1 expression in tumor cells, immune cells, or both has been introduced as predictive biomarker in several clinical trials, shortcomings and limitations of this approach were quickly recognized. As a single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer, various genetic determinants of therapy success, including microsatellite instability, mutational burden, and PD-L1 amplification, are being investigated...
August 2017: Genes, Chromosomes & Cancer
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