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https://www.readbyqxmd.com/read/27926518/higher-programmed-cell-death-1-ligand-1-pd-l1-mrna-level-in-clear-cell-renal-cell-carcinomas-is-associated-with-a-favorable-outcome-due-to-the-active-immune-responses-in-tumor-tissues
#1
Xiang-Hui Ning, Yan-Qing Gong, Shi-Ming He, Teng Li, Jiang-Yi Wang, Shuang-He Peng, Jin-Chao Chen, Jia-Yuan Liu, Nie-Nie Qi, Ying-Lu Guo, Kan Gong
Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27819678/tet2-binds-the-androgen-receptor-and-loss-is-associated-with-prostate-cancer
#2
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/27695045/tumor-specific-epigenetic-silencing-of-corticotropin-releasing-hormone-binding-protein-in-renal-cell-carcinoma-association-of-hypermethylation-and-metastasis
#3
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/27690003/decreased-expression-of-srsf2-splicing-factor-inhibits-apoptotic-pathways-in-renal-cancer
#4
Hanna Kędzierska, Piotr Popławski, Grażyna Hoser, Beata Rybicka, Katarzyna Rodzik, Elżbieta Sokół, Joanna Bogusławska, Zbigniew Tański, Anna Fogtman, Marta Koblowska, Agnieszka Piekiełko-Witkowska
Serine and arginine rich splicing factor 2(SRSF2) belongs to the serine/arginine (SR)-rich family of proteins that regulate alternative splicing. Previous studies suggested that SRSF2 can contribute to carcinogenic processes. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, highly aggressive and difficult to treat, mainly due to resistance to apoptosis. In this study we hypothesized that SRSF2 contributes to the regulation of apoptosis in ccRCC. Using tissue samples obtained from ccRCC patients, as well as independent validation on The Cancer Genome Atlas (TCGA) data, we demonstrate for the first time that expression of SRSF2 is decreased in ccRCC tumours when compared to non-tumorous control tissues...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27663598/overexpression-of-functional-slc6a3-in-clear-cell-renal-cell-carcinoma
#5
Jennifer Hansson, David Lindgren, Helén Nilsson, Elinn Johansson, Martin Johansson, Lena Gustavsson, Hakan Axelson
PURPOSE: Renal cell carcinoma (RCC) is derived from a tissue with a remarkable capacity for vectorial transport. We therefore performed an unbiased exploration of transporter proteins in normal kidney and kidney cancer in order to discover novel clinical targets. EXPERIMENTAL DESIGN: Using the TCGA database we investigated differences in membrane transporter expression in ccRCC and normal kidney. We identified the dopamine transporter SLC6A3 as a specific biomarker for ccRCC...
September 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27574806/kinase-gene-expression-profiling-of-metastatic-clear-cell-renal-cell-carcinoma-tissue-identifies-potential-new-therapeutic-targets
#6
Pooja Ghatalia, Eddy S Yang, Brittany N Lasseigne, Ryne C Ramaker, Sara J Cooper, Dongquan Chen, Sunil Sudarshan, Shi Wei, Arjun S Guru, Amy Zhao, Tiffiny Cooper, Deborah L Della Manna, Gurudatta Naik, Richard M Myers, Guru Sonpavde
Kinases are therapeutically actionable targets. Kinase inhibitors targeting vascular endothelial growth factor receptors (VEGFR) and mammalian target of rapamycin (mTOR) improve outcomes in metastatic clear cell renal cell carcinoma (ccRCC), but are not curative. Metastatic tumor tissue has not been comprehensively studied for kinase gene expression. Paired intra-patient kinase gene expression analysis in primary tumor (T), matched normal kidney (N) and metastatic tumor tissue (M) may assist in identifying drivers of metastasis and prioritizing therapeutic targets...
2016: PloS One
https://www.readbyqxmd.com/read/27556922/an-integrative-genomics-approach-for-identifying-novel-functional-consequences-of-pbrm1-truncated-mutations-in-clear-cell-renal-cell-carcinoma-ccrcc
#7
Yuanyuan Wang, Xingyi Guo, Michael J Bray, Zhiyong Ding, Zhongming Zhao
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer. Recent large-scale next-generation sequencing analyses reveal that PBRM1 is the second most frequently mutated gene harboring many truncated mutations and has a suspected tumor suppressor role in ccRCC. However, the biological consequences of PBRM1 somatic mutations (e.g., truncated mutations) that drive tumor progression in ccRCC remain unclear. METHODS: In this study, we proposed an integrative genomics approach to explore the functional consequences of PBRM1 truncated mutations in ccRCC by incorporating somatic mutations, mRNA expression, DNA methylation, and microRNA (miRNA) expression profiles from The Cancer Genome Atlas (TCGA)...
August 22, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27549193/comprehensive-analyses-of-tumor-immunity-implications-for-cancer-immunotherapy
#8
Bo Li, Eric Severson, Jean-Christophe Pignon, Haoquan Zhao, Taiwen Li, Jesse Novak, Peng Jiang, Hui Shen, Jon C Aster, Scott Rodig, Sabina Signoretti, Jun S Liu, X Shirley Liu
BACKGROUND: Understanding the interactions between tumor and the host immune system is critical to finding prognostic biomarkers, reducing drug resistance, and developing new therapies. Novel computational methods are needed to estimate tumor-infiltrating immune cells and understand tumor-immune interactions in cancers. RESULTS: We analyze tumor-infiltrating immune cells in over 10,000 RNA-seq samples across 23 cancer types from The Cancer Genome Atlas (TCGA). Our computationally inferred immune infiltrates associate much more strongly with patient clinical features, viral infection status, and cancer genetic alterations than other computational approaches...
August 22, 2016: Genome Biology
https://www.readbyqxmd.com/read/27512621/weighted-k-means-support-vector-machine-for-cancer-prediction
#9
SungHwan Kim
To date, the support vector machine (SVM) has been widely applied to diverse bio-medical fields to address disease subtype identification and pathogenicity of genetic variants. In this paper, I propose the weighted K-means support vector machine (wKM-SVM) and weighted support vector machine (wSVM), for which I allow the SVM to impose weights to the loss term. Besides, I demonstrate the numerical relations between the objective function of the SVM and weights. Motivated by general ensemble techniques, which are known to improve accuracy, I directly adopt the boosting algorithm to the newly proposed weighted KM-SVM (and wSVM)...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27390595/met-inhibition-in-clear-cell-renal-cell-carcinoma
#10
Zuoquan Xie, Young H Lee, Marta Boeke, Lucia B Jilaveanu, Zongzhi Liu, Donald P Bottaro, Harriet M Kluger, Brian Shuch
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer. Small molecule VEGFR inhibitors are widely used but are not curative and various resistance mechanisms such as activation of the MET pathway have been described. Dual MET/VEGFR2 inhibitors have recently shown clinical benefit but limited preclinical data evaluates their effects in ccRCC. METHODS: An interrogation of the Cancer Genome Atlas (TCGA) dataset was performed to evaluate oncogenic alterations in the MET/VEGFR2 pathway...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27383829/asymmetric-cancer-hallmarks-in-breast-tumors-on-different-sides-of-the-body
#11
Emanuel M Campoy, Sergio R Laurito, María T Branham, Guillermo Urrutia, Angela Mathison, Francisco Gago, Javier Orozco, Raul Urrutia, Luis S Mayorga, María Roqué
During the last decades it has been established that breast cancer arises through the accumulation of genetic and epigenetic alterations in different cancer related genes. These alterations confer the tumor oncogenic abilities, which can be resumed as cancer hallmarks (CH). The purpose of this study was to establish the methylation profile of CpG sites located in cancer genes in breast tumors so as to infer their potential impact on 6 CH: i.e. sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, induction of angiogenesis, genome instability and invasion and metastasis...
2016: PloS One
https://www.readbyqxmd.com/read/27366943/a-pan-cancer-analysis-of-myc-pvt1-reveals-cnv-unmediated-deregulation-and-poor-prognosis-in-renal-carcinoma
#12
Ioana Posa, Silvia Carvalho, Joana Tavares, Ana Rita Grosso
The PVT1 lncRNA has recently been involved in tumorigenesis by affecting the protein stability of the MYC proto-oncogene. Both MYC and PVT1 reside in a well-known cancer-risk locus and enhanced levels of their products have been reported in different human cancers. Nonetheless, the extension and relevance of the MYC-PVT1 deregulation in tumorigenesis has not yet been systematically addressed.Here we performed a pan-cancer analysis of matched copy number, transcriptomic, methylation, proteomic and clinicopathological profiles for almost 7000 patients from 17 different cancers represented in the TCGA cohorts...
July 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27364684/a-high-resolution-transcriptome-map-of-cell-cycle-reveals-novel-connections-between-periodic-genes-and-cancer
#13
Daniel Dominguez, Yi-Hsuan Tsai, Nicholas Gomez, Deepak Kumar Jha, Ian Davis, Zefeng Wang
Progression through the cell cycle is largely dependent on waves of periodic gene expression, and the regulatory networks for these transcriptome dynamics have emerged as critical points of vulnerability in various aspects of tumor biology. Through RNA-sequencing of human cells during two continuous cell cycles (>2.3 billion paired reads), we identified over 1 000 mRNAs, non-coding RNAs and pseudogenes with periodic expression. Periodic transcripts are enriched in functions related to DNA metabolism, mitosis, and DNA damage response, indicating these genes likely represent putative cell cycle regulators...
August 2016: Cell Research
https://www.readbyqxmd.com/read/27319973/itraq-based-quantitative-proteomic-analysis-reveals-potential-early-diagnostic-markers-of-clear-cell-renal-cell-carcinoma
#14
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
https://www.readbyqxmd.com/read/27198045/glycosyltransferase-gene-expression-profiles-classify-cancer-types-and-propose-prognostic-subtypes
#15
Jahanshah Ashkani, Kevin J Naidoo
Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27197178/burden-of-nonsynonymous-mutations-among-tcga-cancers-and-candidate-immune-checkpoint-inhibitor-responses
#16
Leandro M Colli, Mitchell J Machiela, Timothy A Myers, Lea Jessop, Kai Yu, Stephen J Chanock
Immune checkpoint inhibitor treatment represents a promising approach toward treating cancer and has been shown to be effective in a subset of melanoma, non-small cell lung cancer (NSCLC), and kidney cancers. Recent studies have suggested that the number of nonsynonymous mutations (NsM) can be used to select melanoma and NSCLC patients most likely to benefit from checkpoint inhibitor treatment. It is hypothesized that a higher burden of NsM generates novel epitopes and gene products, detected by the immune system as foreign...
July 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27109935/pan-cancer-subtyping-in-a-2d-map-shows-substructures-that-are-driven-by-specific-combinations-of-molecular-characteristics
#17
Erdogan Taskesen, Sjoerd M H Huisman, Ahmed Mahfouz, Jesse H Krijthe, Jeroen de Ridder, Anja van de Stolpe, Erik van den Akker, Wim Verheagh, Marcel J T Reinders
The use of genome-wide data in cancer research, for the identification of groups of patients with similar molecular characteristics, has become a standard approach for applications in therapy-response, prognosis-prediction, and drug-development. To progress in these applications, the trend is to move from single genome-wide measurements in a single cancer-type towards measuring several different molecular characteristics across multiple cancer-types. Although current approaches shed light on molecular characteristics of various cancer-types, detailed relationships between patients within cancer clusters are unclear...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27010573/intrinsic-genomic-differences-between-african-american-and-white-patients-with-clear-cell-renal-cell-carcinoma
#18
Bhavani Krishnan, Tracy L Rose, Jordan Kardos, Matthew I Milowsky, William Y Kim
Importance: There are well-documented racial disparities in outcomes for African American patients with clear cell renal cell carcinoma (ccRCC). Despite a dramatic improvement in overall survival in white patients since the advent of targeted therapy, survival for African Americans with advanced ccRCC has not changed. There is little known about potential racial differences in tumor biology of ccRCC. Objective: To determine if there are racial differences in the somatic mutation rate and gene expression of ccRCC tumors from white and African American patients...
March 24, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/26865844/expressional-subpopulation-of-cancers-determined-by-g64-a-co-regulated-module
#19
Jae-Woong Min, Sun Shim Choi
Studies of cancer heterogeneity have received considerable attention recently, because the presence or absence of resistant sub-clones may determine whether or not certain therapeutic treatments are effective. Previously, we have reported G64, a co-regulated gene module composed of 64 different genes, can differentiate tumor intra- or inter-subpopulations in lung adenocarcinomas (LADCs). Here, we investigated whether the G64 module genes were also expressed distinctively in different subpopulations of other cancers...
December 2015: Genomics & Informatics
https://www.readbyqxmd.com/read/26855131/the-utility-of-tetraspanin-cd9-as-a-biomarker-for-metastatic-clear-cell-renal-cell-carcinoma
#20
Jo M Garner, Michael J Herr, Kurt B Hodges, Lisa K Jennings
The use of tetraspanin CD9 as a biomarker for renal cell carcinomas (RCC) has been explored with minor conclusions. Identification of a biomarker that not only distinguishes between the different types of renal cell carcinomas, but also predicts the metastatic potential of these tumors would significantly advance diagnosis and prognosis of kidney cancers. We utilized established cell lines to better understand the contribution of CD9 to the metastatic potential of clear cell renal cell carcinomas, and then applied our findings to the TCGA database and immunohistochemical analysis of human samples based on tumor grading to determine the utility of CD9 as a biomarker for RCC...
February 26, 2016: Biochemical and Biophysical Research Communications
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