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The cancer genome atlas

Yingjie Shao, Dachuan Zhang, Xiaodong Li, Jing Yang, Lujun Chen, Zhonghua Ning, Yun Xu, Guohua Deng, Min Tao, Yibei Zhu, Jingting Jiang
BACKGROUND: It has been reported that B-cell-specific moloney leukemia virus insertion site 1 (Bmi-1) has important roles in various cancers, but its regulation through microRNAs (miRNAs) and its functions in hepatocellular carcinoma (HCC) remains unclear. METHODS: We investigated Bmi-1 expression and its prognostic significance in HCC by using tissue samples and The Cancer Genome Atlas (TCGA) datasets. The relationship between miRNAs and Bmi-1 was verified by bioinformatics prediction and immunofluorescence...
June 15, 2018: Molecular Pharmaceutics
Eleonora Sementino, Craig W Menges, Yuwaraj Kadariya, Suraj Peri, Jinfei Xu, Zemin Liu, Richard G Wilkes, Kathy Q Cai, Frank J Rauscher, Andres J Klein-Szanto, Joseph R Testa
Malignant mesothelioma (MM) is a therapy-resistant cancer arising primarily from the lining of the pleural and peritoneal cavities. The most frequently altered genes in human MM are cyclin-dependent kinase inhibitor 2A (CDKN2A), which encodes components of the p53 (p14ARF) and RB (p16INK4A) pathways, BRCA1-associated protein 1 (BAP1), and neurofibromatosis 2 (NF2). Furthermore, the p53 gene (TP53) itself is mutated in ~15% of MMs. In many MMs, the PI3K-PTEN-AKT-mTOR signaling node is hyperactivated, which contributes to tumor cell survival and therapeutic resistance...
June 15, 2018: Journal of Cellular Physiology
Juan M Barajas, Ryan Reyes, Maria J Guerrero, Samson T Jacob, Tasneem Motiwala, Kalpana Ghoshal
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Thus, a better understanding of molecular aberrations involved in HCC pathogenesis is necessary for developing effective therapy. It is well established that cancer cells metabolize energy sources differently to rapidly generate biomass. Glucose-6-phosphate-dehydrogenase (G6PD), the rate-limiting enzyme of the Pentose Phosphate Pathway (PPP), is often activated in human malignancies to generate precursors for nucleotide and lipid synthesis...
June 14, 2018: Scientific Reports
Sun Wu, Yifeng Dai, Yuan Zhang, Xiufeng Wang, Lihua Wang, Dong Ma, Lingxiu Zhang, Yifan Pang, Yang Jiao, Mingshan Niu, Kailin Xu, Xiaoyan Ke, Jinlong Shi, Zhiheng Cheng, Lin Fu
The mutational spectrum and prognostic stratification of intermediate-risk acute myeloid leukemia (IR-AML), which accounts for a substantial number of AML, are unclear. In order to explore the prognostic significance of the mutational spectrum in IR-AML, 106 IR-AML patients were collected from The Cancer Genome Atlas database. Sixty-two patients underwent chemotherapy-only, forty-four proceeded to allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fifty-five patients had more than five recurrent genetic mutations...
June 15, 2018: Cancer Gene Therapy
Shengmeng Peng, Tao Du, Wanhua Wu, Xianju Chen, Yiming Lai, Dingjun Zhu, Qiong Wang, Xiaoming Ma, Chunhao Lin, Zean Li, Zhenghui Guo, Hai Huang
PURPOSE: The aim of this study was to investigate the associations of serine proteinase inhibitor family G1 (SERPING1) down-regulation with poor prognosis in patients with prostate cancer (PCa). Furthermore, we aim to find more novel and effective PCa molecular markers to provide an early screening of PCa, distinguish patients with aggressive PCa, predict the prognosis, or reduce the economic burden of PCa. METHODS: SERPING1 protein expression in both human PCa and normal prostate tissues was detected by immunohistochemical staining, which intensity was analyzed in association with clinical pathological parameters such Gleason score, pathological grade, clinical stage, tumor stage, lymph node metastasis, and distant metastasis...
June 11, 2018: Urologic Oncology
Mingsheng Guo, Wei Yue, David C Samuels, Hui Yu, Jing He, Ying-Yong Zhao, Yan Guo
Genotyping arrays characterize genome-wide SNPs for a study cohort and were the primary technology behind genome wide association studies over the last decade. The Cancer Genome Atlas (TCGA) is one of the largest cancer consortium studies, and it collected genotyping data for all of its participants. Using TCGA SNP data genotyped using the Affymetrix 6.0 SNP array from 12,064 samples, we conducted a comprehensive comparisons across DNA sources (tumor tissue, normal tissue, and blood) and sample storage protocols (formalin-fixed paraffin-embedded (FFPE) vs...
June 11, 2018: Genomics
Chenggong Hu, Yongfang Zhou, Chang Liu, Yan Kang
Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-associated mortality worldwide. In the current study, comprehensive bioinformatic analyses were performed to develop a novel scoring system for GC risk assessment based on CAP-Gly domain containing linker protein family member 4 (CLIP4) DNA methylation status. Two GC datasets with methylation sequencing information and mRNA expression profiling were downloaded from the The Cancer Genome Atlas and Gene Expression Omnibus databases...
June 6, 2018: International Journal of Oncology
Meng Zhang, Yu Pan, Ranran Jiang, Pingfu Hou, Haixia Shan, Fang Chen, Tao Jiang, Jin Bai, Junnian Zheng
DKC1, an X‑linked gene encoding dyskerin at Xq28, is a crucial component of the telomerase complex and is indispensable for normal telomere function and the post‑-transcriptional modification of precursor rRNA. It has been revealed to exert diverse biological functions and prognostic values in numerous types of cancers. Our present study was aimed at examining DKC1 expression in normal renal tissues and clear cell renal cell carcinoma (ccRCC) samples and the prognostic value of DKC1 in ccRCC. We examined DKC1 protein expression levels in tissue microarrays including 307 cases of ccRCC tissues and in 75 pairs of ccRCC and paracancerous tissues with immunohistochemistry...
June 11, 2018: Oncology Reports
Fangce Wang, Xiaoxue Tian, Jie Zhou, Guangming Wang, Wenlei Yu, Zheng Li, Zhuoyi Fan, Wenjun Zhang, Aibin Liang
Long non-coding RNAs (lncRNAs) are transcripts characterized by >200 nucleotides, without validated protein production. Previous studies have demonstrated that certain lncRNAs have a critical role in the initiation and development of acute myeloid leukemia (AML). In the present study, the subtype‑specific lncRNAs in AML was identified. Following the exclusion of the subtype‑specific lncRNAs, the prognostic value of lncRNAs was investigated and a three‑lncRNA expression‑based risk score [long intergenic non‑protein coding RNA 926, family with sequence similarity 30 member A and LRRC75A antisense RNA 1 (LRRC75A‑AS1)] was developed for AML patient prognosis prediction by analyzing the RNA‑seq data of AML patients from Therapeutically Available Research to Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) projects...
June 6, 2018: Molecular Medicine Reports
Xia Liu, Luwei Wei, Bingbing Zhao, Xiangxue Cai, Caihua Dong, Fuqiang Yin
Drug resistance is a principal contributor to the poor prognosis of ovarian cancer (OC). Therefore, identifying factors that affect drug resistance in OC is critical. In the present study, 51 OC specimens from lab collections were immunohistochemically tested, public data for 489 samples from The Cancer Genome Atlas cohort and 1,656 samples from the Kaplan‑Meier Plotter were downloaded, and data were retrieved from Oncomine. It was identified that the mRNA and protein expression of the potassium calcium‑activated channel subfamily N member 3 (KCNN3) was markedly lower in OC tissues compared with normal tissues, and in drug‑resistant OC tissues compared with sensitive OC tissues...
May 31, 2018: Molecular Medicine Reports
Satoshi Sugita, Hideki Enokida, Hirofumi Yoshino, Kazutaka Miyamoto, Masaya Yonemori, Takashi Sakaguchi, Yoichi Osako, Masayuki Nakagawa
The active form of the small GTPase RAS binds to downstream effectors to promote cell growth and proliferation. RAS signal enhancement contributes to tumorigenesis, invasion, and metastasis in various different cancers. HRAS proto-oncogene GTPase (HRAS), one of the RAS isoforms, was the first human oncogene for which mutations were reported in T24 bladder cancer (BC) cells in 1982, and HRAS mutation or upregulation has been reported in several cancers. According to data from The Cancer Genome Atlas, HRAS expression was significantly upregulated in clinical BC samples compared to healthy samples (P=0...
June 11, 2018: International Journal of Oncology
Ting-Ting Zhang, Ning Qu, Guo-Hua Sun, Long Zhang, Yuan-Jin Wang, Xiang-Ming Mu, Wen-Jun Wei, Yu-Long Wang, Yu Wang, Qing-Hai Ji, Yong-Xue Zhu, Rong-Liang Shi
Thyroid cancer is a common endocrine cancer, of which papillary thyroid cancer (PTC) is the most common type. Neuregulin 1 (NRG1), a glycoprotein mediating cell‑cell signaling, plays vital roles in cellular activities; however, its role in PTC progression remains poorly understood. In this study, we performed immunohistochemistry in 196 samples from patients and found that NRG1, a potential prognostic marker is highly expressed in PTC compared with adjacent normal tissues. Cell Counting kit‑8 (CCK‑8) and clone formation assays indicated that NRG1 is essential for PTC cell viability and proliferation, probably by regulating redox homeostasis, which was implied by ROS generation analysis and intracellular GSH activity assay...
May 31, 2018: International Journal of Oncology
Joseph DiDomenico, Jonathan B Lamano, Daniel Oyon, Yuping Li, Dorina Veliceasa, Gurvinder Kaur, Leonel Ampie, Winward Choy, Jason B Lamano, Orin Bloch
Glioblastoma (GBM) promotes immunosuppression through upregulation of PD-L1 and regulatory T cell (Treg) expansion, but the association of these suppressive factors has not been well elucidated. Here, we investigate a role of PD-L1 in expanding Tregs and the value of targeting the PD-1 receptor to inhibit Treg expansion. Quantitative RNA sequencing data from The Cancer Genome Atlas were evaluated for an association between CD274 and FOXP3 transcript expressions and impact of FOXP3 on clinical outcomes. Peripheral leukocytes from patients with newly diagnosed GBM were profiled for PD-L1+ myeloid expressions and Treg abundance...
2018: Oncoimmunology
Chaoju Gong, Jie Shen, Zejun Fang, Lei Qiao, Ruifang Feng, Xianmi Lin, Suyan Li
Uveal melanoma (UM) is the most common primary intraocular tumor in adults and it carries a high risk of metastasis and mortality. Various pro-inflammatory cytokines have been found to be significantly increased in the aqueous humor or vitreous fluid of UM patients; however, the role of these cytokines in UM metastasis remains elusive. In this study, we found that long-term IL-6 exposure promoted the migration and invasion of UM cells, diminished cell-cell adhesion, and enhanced focal adhesion. Moreover, IL-6 treatment decreased the membranous epithelial marker TJP1 and increased the cytoplasmic mesenchymal marker Vimentin...
June 13, 2018: Bioscience Reports
Hui Shen, Juliann Shih, Daniel P Hollern, Linghua Wang, Reanne Bowlby, Satish K Tickoo, Vésteinn Thorsson, Andrew J Mungall, Yulia Newton, Apurva M Hegde, Joshua Armenia, Francisco Sánchez-Vega, John Pluta, Louise C Pyle, Rohit Mehra, Victor E Reuter, Guilherme Godoy, Jeffrey Jones, Carl S Shelley, Darren R Feldman, Daniel O Vidal, Davor Lessel, Tomislav Kulis, Flavio M Cárcano, Kristen M Leraas, Tara M Lichtenberg, Denise Brooks, Andrew D Cherniack, Juok Cho, David I Heiman, Katayoon Kasaian, Minwei Liu, Michael S Noble, Liu Xi, Hailei Zhang, Wanding Zhou, Jean C ZenKlusen, Carolyn M Hutter, Ina Felau, Jiashan Zhang, Nikolaus Schultz, Gad Getz, Matthew Meyerson, Joshua M Stuart, Rehan Akbani, David A Wheeler, Peter W Laird, Katherine L Nathanson, Victoria K Cortessis, Katherine A Hoadley
We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma...
June 12, 2018: Cell Reports
A Fu, H R Chang, Z F Zhang
Increasingly affordable high-throughput molecular profiling technologies have made feasible the measurement of omics-wide interindividual variations for the purposes of predicting cancer prognosis. While multiple types of genetic, epigenetic, and expression changes have been implicated in ovarian cancer, existing prognostic biomarker strategies are constrained to analyzing single classes of molecular variations. The extra predictive power afforded by the integration of multiple omics types remains largely unexplored...
April 20, 2018: Carcinogenesis
Pawel Karpinski, Arpad Patai, Wojciech Hap, Wojciech Kielan, Izabela Laczmanska, Maria Malgorzata Sasiadek
AIM: We aimed to assess to what extent CpG island methylator phenotype (CIMP) contributes to cancer subtypes obtained by multilevel omic data analysis. MATERIALS & METHODS: 16 The Cancer Genome Atlas datasets encompassing three data layers in 4688 tumor samples were analyzed. We identified cancer integrative subtypes (ISs) by the use of similarity network fusion and consensus clustering. CIMP high (CIMP-H) associated ISs were profiled by gene sets and transcriptional regulators enrichment analysis...
June 13, 2018: Epigenomics
Rola M Saleeb, Mina Farag, Zsuzsanna Lichner, Fadi Brimo, Jenni Bartlett, Georg Bjarnason, Antonio Finelli, Fabio Rontondo, Michelle R Downes, George M Yousef
Papillary renal cell carcinoma (PRCC) is the most common non-clear cell RCCs and is known to comprise two histological subtypes. PRCC2 is more aggressive and is molecularly distinct from the other subtypes. Despite this PRCCs are treated together as one entity, and they show poor response to the current therapies that do not target pathways implicated in their pathogenesis. We have previously detected ABCC2 (an ABC transporter), VEGF and mTOR pathways to be enriched in PRCC2. In this study, we assess the therapeutic potential of targeting these pathways in PRCC2...
June 13, 2018: Molecular Oncology
Masashi Fukayama, Akiko Kunita, Atsushi Kaneda
Epstein-Barr virus-associated gastric cancer (EBVaGC) is a representative EBV-infected epithelial neoplasm, which is now included as one of the four subtypes of The Cancer Genome Atlas molecular classification of gastric cancer. In this review, we portray a gastritis-infection-cancer sequence of EBVaGC. This virus-associated type of gastric cancer demonstrates clonal growth of EBV-infected epithelial cells within the mucosa of atrophic gastritis. Its core molecular abnormality is the EBV-specific hyper-epigenotype of CpG island promoter methylation, which induces silencing of tumor suppressor genes...
2018: Advances in Experimental Medicine and Biology
Shixuan Shen, Xiaohui Chen, Hao Li, Liping Sun, Yuan Yuan
Background: The promoter methylation of MLH1 gene and gastric cancer (GC)has been investigated previously. To get a more credible conclusion, we performed a systematic review and meta and bioinformatic analysis to clarify the role of MLH1 methylation in the prediction and prognosis of GC. Methods: Eligible studies were targeted after searching the PubMed, Web of Science, Embase, BIOSIS, CNKI and Wanfang Data to collect the information of MLH1 methylation and GC. The link strength between the two was estimated by odds ratio with its 95% confidence interval...
2018: Journal of Cancer
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