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      Methylation-driven genes PMPCAP1, SOWAHC and ZNF454 as potential prognostic biomarkers in lung squamous cell carcinoma

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          Abstract

          Of the different types of lung cancer, lung squamous cell cancer (LUSC) has the second highest rates of morbidity and mortality, which have been increasing in recent years. Epigenetic abnormalities may serve as potential biomarkers and diagnostic and/or therapeutic targets, which may help to monitor and improve the prognosis of patients with cancer. In the present study, data were obtained from The Cancer Genome Atlas database and survival and joint survival analyses were conducted using the R MethylMix package. Peptidase, mitochondrial processing a subunit pseudogene 1 (PMPCAP1), sosondowah ankyrin repeat domain family member C (SOWAHC) and zinc finger protein (ZNF) 454 were identified as independent prognosis-related hub methylation-driven genes (MDGs). Of these three genes, PMPCAP1 and SOWAHC, characterized by hypomethylation and high expression levels, were associated with poor prognosis in patients with LUSC, whilst ZNF454 was associated with an improved prognosis. In addition, pathway enrichment analysis suggested that PMPCAP1, SOWAHC and ZNF454 were primarily involved in gene expression or transcription pathways. Furthermore, 5, 1 and 10 key methylation sites of PMPCAP1, SOWAHC and ZNF454, respectively, were confirmed to be significantly relevant to gene expression, establishing a basis for further investigation into the mechanisms and more precise targets of these 3 genes. In conclusion, the MDGs PMPCAP1, SOWAHC and ZNF454 may be potential prognostic biomarkers of LUSC for guiding diagnosis and therapy options, as well as providing a theoretical basis for further investigation.

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          Most cited references35

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          A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

          The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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            High density DNA methylation array with single CpG site resolution.

            We have developed a new generation of genome-wide DNA methylation BeadChip which allows high-throughput methylation profiling of the human genome. The new high density BeadChip can assay over 480K CpG sites and analyze twelve samples in parallel. The innovative content includes coverage of 99% of RefSeq genes with multiple probes per gene, 96% of CpG islands from the UCSC database, CpG island shores and additional content selected from whole-genome bisulfite sequencing data and input from DNA methylation experts. The well-characterized Infinium® Assay is used for analysis of CpG methylation using bisulfite-converted genomic DNA. We applied this technology to analyze DNA methylation in normal and tumor DNA samples and compared results with whole-genome bisulfite sequencing (WGBS) data obtained for the same samples. Highly comparable DNA methylation profiles were generated by the array and sequencing methods (average R2 of 0.95). The ability to determine genome-wide methylation patterns will rapidly advance methylation research. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Cytoscape.js: a graph theory library for visualisation and analysis

              Summary: Cytoscape.js is an open-source JavaScript-based graph library. Its most common use case is as a visualization software component, so it can be used to render interactive graphs in a web browser. It also can be used in a headless manner, useful for graph operations on a server, such as Node.js. Availability and implementation: Cytoscape.js is implemented in JavaScript. Documentation, downloads and source code are available at http://js.cytoscape.org. Contact: gary.bader@utoronto.ca
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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
                March 2020
                13 January 2020
                13 January 2020
                : 21
                : 3
                : 1285-1295
                Affiliations
                [1 ]School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250022, P.R. China
                [2 ]Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
                [3 ]Department of Oncology, Zibo Maternal and Child Health Hospital, Zibo, Shandong 255000, P.R. China
                [4 ]Department of Oncology, Yun Cheng Country People's Hospital, Heze, Shandong 274700, P.R. China
                [5 ]Department of Oncology, Chang Qing District People's Hospital, Jinan, Shandong 250300, P.R. China
                [6 ]Basic Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
                Author notes
                Correspondence to: Dr Jie Liu, Department of Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Huaiyin, Jinan, Shandong 250117, P.R. China, E-mail: wzzljsb123@ 123456126.com
                Dr Jia Wang, Department of Oncology, Zibo Maternal and Child Health Hospital, 11 Xingyuan East Road, Zhangdian, Zibo, Shandong 255000, P.R. China, E-mail: wj_wzzlj@ 123456126.com
                Article
                mmr-21-03-1285
                10.3892/mmr.2020.10933
                7002985
                32016477
                7fb0332f-5744-4cb4-876d-7b9841f57aed
                Copyright: © Zhu 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
                : 13 June 2019
                : 18 December 2019
                Categories
                Articles

                lung squamous cell carcinoma,methylation-driven genes,the cancer genome atlas,methylmix,biomarker,prognosis

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