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      Identification of a stool long non‐coding RNAs panel as a potential biomarker for early detection of colorectal cancer

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          Abstract

          Background

          The feces of colorectal cancer (CRC) patients contain tumor colonocytes, which constantly shed into the lumen area. Therefore, stool evaluation can be considered as a rapid and low‐risk way to directly determine the colon and rectum status. As long non‐coding RNAs (lncRNAs) alterations are important in cancer cells fate regulation, we aimed to assess the level of a panel of cancer‐related lncRNAs in fecal colonocytes.

          Methods

          The population study consisted of 150 subjects, including a training set, a validation set, and a group of 30 colon polyps. The expression levels of lncRNAs were evaluated by quantitative real‐time PCR (qRT‐PCR). The NPInetr and EnrichR tools were used to identify the interactions and functions of lncRNAs.

          Results

          A total of 10 significantly dysregulated lncRNAs, including CCAT1, CCAT2, H19, HOTAIR, HULC, MALAT1, PCAT1, MEG3, PTENP1, and TUSC7, were chosen for designing a predictive panel. The diagnostic performance of the panel in distinguishing CRCs from the healthy group was AUC: 0.8554 in the training set and 0.8465 in the validation set. The AUC for early CRCs (I‐II TNM stages) was 0.8554 in the training set and 0.8465 in the validation set, and for advanced CRCs (III‐IV TNM stages) were 0.9281 in the training set and 0.9236 in the validation set. The corresponding AUC for CRCs vs polyps were 0.9228 (I‐IV TNM stages), 0.9042 (I‐II TNM stages), and 0.9362 (III‐IV TNM stages).

          Conclusions

          These data represented the application of analysis of fecal colonocytes lncRNAs in early detection of CRC.

          Abstract

          The expression profile of fecal lncRNAs in the training set. (A) Hierarchical clustering of fecal lncRNAs expression pattern of training set. The hierarchical clustering was designed with 30 differently expressed lncRNAs in 30 colorectal cancer (CRC) cases and 30 healthy controls. The clustering of lncRNAs placed in entire samples. (B) Pairwise comparison of lncRNAs in the training set. Normal samples were considered as controls, and their expression level values were considered as 1. The Mann‐Whitney U test was used to assess the differences of LncRNAs level between groups. The relative expression was considered as significant when <0.5 or >2.

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          Most cited references35

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            Is Open Access

            ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks

            Summary: We have developed ClueGO, an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes. ClueGO integrates Gene Ontology (GO) terms as well as KEGG/BioCarta pathways and creates a functionally organized GO/pathway term network. It can analyze one or compare two lists of genes and comprehensively visualizes functionally grouped terms. A one-click update option allows ClueGO to automatically download the most recent GO/KEGG release at any time. ClueGO provides an intuitive representation of the analysis results and can be optionally used in conjunction with the GOlorize plug-in. Availability: http://www.ici.upmc.fr/cluego/cluegoDownload.shtml Contact: jerome.galon@crc.jussieu.fr Supplementary information: Supplementary data are available at Bioinformatics online.
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              Long noncoding RNA as modular scaffold of histone modification complexes.

              Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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                Author and article information

                Contributors
                Ehsanmojarad@gmail.com , E.nazemalhosseini@sbmu.ac.ir
                Journal
                J Clin Lab Anal
                J Clin Lab Anal
                10.1002/(ISSN)1098-2825
                JCLA
                Journal of Clinical Laboratory Analysis
                John Wiley and Sons Inc. (Hoboken )
                0887-8013
                1098-2825
                23 October 2020
                February 2021
                : 35
                : 2 ( doiID: 10.1002/jcla.v35.2 )
                : e23601
                Affiliations
                [ 1 ] Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran
                [ 2 ] Gastroenterology and Liver Diseases Research Center Research Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran
                [ 3 ] Molecular Genetics Department Genomic Research Center Shahid Beheshti University of Medical Sciences Tehran Iran
                [ 4 ] Department of Genetics Faculty of Advanced Science and Technology Tehran Medical Sciences Islamic Azad University Tehran Iran
                Author notes
                [*] [* ] Correspondence

                Ehsan Nazemalhosseini‐Mojarad, Gastroenterology and Liver Disease Research center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Yeman St, Chamran Expressway, P.O. Box 19857‐17411, Tehran, Iran.

                Emails: Ehsanmojarad@ 123456gmail.com ; E.nazemalhosseini@ 123456sbmu.ac.ir

                Author information
                https://orcid.org/0000-0001-8914-004X
                https://orcid.org/0000-0001-9599-6151
                https://orcid.org/0000-0002-9382-9840
                Article
                JCLA23601
                10.1002/jcla.23601
                7891513
                33094859
                bdc354f3-b047-417d-aa6d-003d2fea8369
                © 2020 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 May 2020
                : 06 September 2020
                : 09 September 2020
                Page count
                Figures: 5, Tables: 4, Pages: 10, Words: 6123
                Funding
                Funded by: The authors gratefully acknowledge the Research Institute for Gastroenterology and Liver Diseases of the Shahid Beheshti University of Medical Sciences (RIGLD), for its support of this study , open-funder-registry 10.13039/501100005851;
                Award ID: 949
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:18.02.2021

                Clinical chemistry
                biomarker,colorectal cancer,fecal colonocytes,gene expression,long non‐coding rnas

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