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https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#1
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29180475/distinct-tp63-isoform-driven-transcriptional-signatures-predict-tumor-progression-and-clinical-outcomes
#2
Hussein Abbas, Ngoc Hoang Bao Bui, Kimal Rajapakshe, Justin Wong, Preethi Gunaratne, Kenneth Y Tsai, Cristian Coarfa, Elsa R Flores
TP63 is required to maintain stem cell pluripotency and suppresses the metastatic potential of cancer cells through multiple mechanisms. These functions are differentially regulated by individual isoforms, necessitating a deeper understanding of how the distinct transcriptional programs controlled by these isoforms affect cancer progression and outcomes. In this study, we conducted a pan-cancer analysis of The Cancer Genome Atlas (TCGA) to identify transcriptional networks regulated by TAp63 and ΔNp63 using transcriptomes derived from epidermal cells of TAp63-/- and ΔNp63-/- mice...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29143738/bladder-cancer-associated-mutations-in-rxra-activate-peroxisome-proliferator-activated-receptors-to-drive-urothelial-proliferation
#3
Angela M Halstead, Chiraag D Kapadia, Jennifer Bolzenius, Clarence E Chu, Andrew Schriefer, Lukas D Wartman, Gregory R Bowman, Vivek K Arora
RXRA regulates transcription as part of a heterodimer with 14 other nuclear receptors, including the peroxisome proliferator-activated receptors (PPARs). Analysis from the TCGA raised the possibility that hyperactive PPAR signaling, either due to PPAR gamma gene amplification or RXRA hot-spot mutation (S427F/Y) drives 20-25% of human bladder cancers. Here we characterize mutant RXRA, demonstrating it induces enhancer/promoter activity in the context of RXRA/PPAR heterodimers in human bladder cancer cells. Structure-function studies indicate that the RXRA substitution allosterically regulates the PPAR AF2 domain via an aromatic interaction with the terminal tyrosine found in PPARs...
November 16, 2017: ELife
https://www.readbyqxmd.com/read/29116491/prognostic-and-predictive-value-of-o-6-methylguanine-methyltransferase-for-chemotherapy-in-patients-with-muscle-invasive-bladder-cancer
#4
Junyu Zhang, Yu Zhu, Yiwei Wang, Qiang Fu, Huyang Xie, Zheng Liu, Hangcheng Fu, Yifan Cao, Jiejie Xu, Bo Dai
PURPOSE: DNA repair genes are potential biomarkers for chemotherapy in muscle-invasive bladder cancer (MIBC). O(6)-methylguanine methyltransferase (MGMT) is involved in DNA repair and is found to affect the efficacy of platinum-based chemotherapy. However, the prognostic or predictive value of MGMT expression in chemotherapy for MIBC is unknown. MATERIALS AND METHODS: Immunohistochemical staining for MGMT was performed in paraffin-embedded tumor tissue of high-grade MIBC patients who underwent cystectomy in two independent cohorts [n = 74 for Fudan University Shanghai Cancer Center (FUSCC) cohort and n = 115 for Zhongshan Hospital (ZS) cohort]...
November 7, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29107929/viral-sequences-in-human-cancer
#5
Paul G Cantalupo, Joshua P Katz, James M Pipas
We have developed a virus detection and discovery computational pipeline, Pickaxe, and applied it to NGS databases provided by The Cancer Genome Atlas (TCGA). We analyzed a collection of whole genome (WGS), exome (WXS), and RNA (RNA-Seq) sequencing libraries from 3052 participants across 22 different cancers. NGS data from nearly all tumor and normal tissues examined contained contaminating viral sequences. Intensive computational and manual efforts are required to remove these artifacts. We found that several different types of cancers harbored Herpesviruses including EBV, CMV, HHV1, HHV2, HHV6 and HHV7...
November 3, 2017: Virology
https://www.readbyqxmd.com/read/29071385/protein-kinase-d-inhibitor-crt0066101-suppresses-bladder-cancer-growth-in-vitro-and-xenografts-via-blockade-of-the-cell-cycle-at-g2-m
#6
Qingdi Quentin Li, Iawen Hsu, Thomas Sanford, Reema Railkar, Navin Balaji, Carole Sourbier, Cathy Vocke, K C Balaji, Piyush K Agarwal
The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer...
October 25, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29050337/comprehensive-immune-transcriptomic-analysis-in-bladder-cancer-reveals-subtype-specific-immune-gene-expression-patterns-of-prognostic-relevance
#7
Runhan Ren, Kathrin Tyryshkin, Charles H Graham, Madhuri Koti, D Robert Siemens
Recent efforts on genome wide profiling of muscle invasive bladder cancer (MIBC) have led to its classification into distinct genomic and transcriptomic molecular subtypes that exhibit variability in prognosis. Evolving evidence from recent immunotherapy trials has demonstrated the significance of pre-existing tumour immune profiles that could guide treatment decisions. To identify immune gene expression patterns associated with the molecular subtypes, we performed a comprehensive in silico immune transcriptomic profiling, utilizing transcriptomic data from 347 MIBC cases from The Cancer Genome Atlas (TCGA)...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29029484/ybx1-promotes-tumor-growth-by-elevating-glycolysis-in-human-bladder-cancer
#8
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
#9
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 19, 2017: Cell
https://www.readbyqxmd.com/read/28977887/risk-score-based-on-three-mrna-expression-predicts-the-survival-of-bladder-cancer
#10
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
#11
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
#12
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...
November 7, 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
#13
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
#14
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
#15
Zhao Yang, Luyun He, Kaisu Lin, Yun Zhang, Aihua Deng, Yong Liang, Chong Li, Tingyi Wen
Purpose: Bladder cancer 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.Experimental Design: In a discovery step, human BCSCs and bladder cancer non-stem cells (BCNSCs) isolated from primary bladder cancer samples #1 and #2, and the bladder cancer 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
#16
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
#17
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
#18
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
#19
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
#20
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
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