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      Identification of prognostic genes in kidney renal clear cell carcinoma by RNA-seq data analysis

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          Abstract

          The present study aimed to analyze RNA-seq data of kidney renal clear cell carcinoma (KIRC) to identify prognostic genes. RNA-seq data were downloaded from The Cancer Genome Atlas. Feature genes with a coefficient of variation (CV) >0.5 were selected using the genefilter package in R. Gene co-expression networks were constructed with the WGCNA package. Cox regression analysis was performed using the survive package. Furthermore, a functional enrichment analysis was conducted using Database for Annotation, Visualization and Integrated Discovery tools. A total of 533 KIRC samples were collected, from which 6,758 feature genes with a CV >0.5 were obtained for further analysis. The KIRC samples were divided into two sets: The training set (n=319 samples) and the validation set (n=214 samples). Subsequently, gene co-expression networks were constructed for the two sets. A total of 12 modules were identified, and the green module was significantly associated with survival time. Genes from the green module were revealed to be implicated in the cell cycle and p53 signaling pathway. In addition, a total of 11 hub genes were revealed, and 10 of them (CCNA2, CDC20, CDCA8, GTSE1, KIF23, KIF2C, KIF4A, MELK, TOP2A and TPX2) were validated as possessing prognostic value, as determined by conducting a survival analysis on another gene expression dataset. In conclusion, a total of 10 prognostic genes were identified in KIRC. These findings may help to advance the understanding of this disease, and may also provide potential biomarkers for therapeutic development.

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          Most cited references28

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          DAVID: Database for Annotation, Visualization, and Integrated Discovery.

          Functional annotation of differentially expressed genes is a necessary and critical step in the analysis of microarray data. The distributed nature of biological knowledge frequently requires researchers to navigate through numerous web-accessible databases gathering information one gene at a time. A more judicious approach is to provide query-based access to an integrated database that disseminates biologically rich information across large datasets and displays graphic summaries of functional information. Database for Annotation, Visualization, and Integrated Discovery (DAVID; http://www.david.niaid.nih.gov) addresses this need via four web-based analysis modules: 1) Annotation Tool - rapidly appends descriptive data from several public databases to lists of genes; 2) GoCharts - assigns genes to Gene Ontology functional categories based on user selected classifications and term specificity level; 3) KeggCharts - assigns genes to KEGG metabolic processes and enables users to view genes in the context of biochemical pathway maps; and 4) DomainCharts - groups genes according to PFAM conserved protein domains. Analysis results and graphical displays remain dynamically linked to primary data and external data repositories, thereby furnishing in-depth as well as broad-based data coverage. The functionality provided by DAVID accelerates the analysis of genome-scale datasets by facilitating the transition from data collection to biological meaning.
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            Kinesins and cancer.

            Kinesins are a family of molecular motors that travel unidirectionally along microtubule tracks to fulfil their many roles in intracellular transport or cell division. Over the past few years kinesins that are involved in mitosis have emerged as potential targets for cancer drug development. Several compounds that inhibit two mitotic kinesins (EG5 (also known as KIF11) and centromere-associated protein E (CENPE)) have entered Phase I and II clinical trials either as monotherapies or in combination with other drugs. Additional mitotic kinesins are currently being validated as drug targets, raising the possibility that the range of kinesin-based drug targets may expand in the future.
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              Genetic basis of kidney cancer: Role of genomics for the development of disease-based therapeutics

              W Linehan (2012)
              Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL , MET , FLCN , fumarate hydratase , succinate dehydrogenase , TSC1 , TSC2 , and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                April 2017
                13 February 2017
                13 February 2017
                : 15
                : 4
                : 1661-1667
                Affiliations
                Department of Urology, The First Hospital of Jiaxing, Jiaxing, Zhejiang 314001, P.R. China
                Author notes
                Correspondence to: Dr Yi He, Department of Urology, The First Hospital of Jiaxing, 1882 South Zhonghuai Road, Nanhu, Jiaxing, Zhejiang 314001, P.R. China, E-mail: heyihdhdhhdd@ 123456hotmail.com
                [*]

                Contributed equally

                Article
                mmr-15-04-1661
                10.3892/mmr.2017.6194
                5364979
                28260099
                5cc0aa39-ac73-49ea-8f52-028004271b23
                Copyright: © Gu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 19 November 2015
                : 06 December 2016
                Categories
                Articles

                kidney renal clear cell carcinoma,gene co-expression network,survival analysis,hub genes

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