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      Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

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          Abstract

          We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin ( POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP ( P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml ( P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.

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          featureCounts: An efficient general-purpose program for assigning sequence reads to genomic features

          , , (2013)
          Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages.
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            Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals.

            Subepithelial fibrosis is a cardinal feature of bronchial asthma. Collagen I, III, and V; fibronectin; and tenascin-C are deposited in the lamina reticularis. Extensive evidence supports the pivotal role of IL-4 and IL-13 in subepithelial fibrosis; however, the precise mechanism remains unclear. We have previously identified the POSTN gene encoding periostin as an IL-4/IL-13-inducible gene in bronchial epithelial cells. Periostin is thought to be an adhesion molecule because it possesses 4 fasciclin I domains. We explore the possibility that periostin is involved in subepithelial fibrosis in bronchial asthma. We analyzed induction of periostin in lung fibroblasts by IL-4 or IL-13. We next analyzed expression of periostin in patients with asthma and in ovalbumin-sensitized and ovalbumin-inhaled mice. Furthermore, we examined the binding ability of periostin to other extracellular matrix proteins. Both IL-4 and IL-13 induced secretion of periostin in lung fibroblasts independently of TGF-beta. Periostin colocalized with other extracellular matrix proteins involved in subepithelial fibrosis in both asthma patients and ovalbumin-sensitized and ovalbumin-inhaled wild-type mice, but not in either IL-4 or IL-13 knockout mice. Periostin had an ability to bind to fibronectin, tenascin-C, collagen V, and periostin itself. Periostin secreted by lung fibroblasts in response to IL-4 and/or IL-13 is a novel component of subepithelial fibrosis in bronchial asthma. Periostin may contribute to this process by binding to other extracellular matrix proteins. Periostin induced by IL-4/IL-13 shows promise in inhibiting subepithelial fibrosis in bronchial asthma.
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              Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients.

              Eosinophilic airway inflammation is heterogeneous in asthmatic patients. We recently described a distinct subtype of asthma defined by the expression of genes inducible by T(H)2 cytokines in bronchial epithelium. This gene signature, which includes periostin, is present in approximately half of asthmatic patients and correlates with eosinophilic airway inflammation. However, identification of this subtype depends on invasive airway sampling, and hence noninvasive biomarkers of this phenotype are desirable. We sought to identify systemic biomarkers of eosinophilic airway inflammation in asthmatic patients. We measured fraction of exhaled nitric oxide (Feno), peripheral blood eosinophil, periostin, YKL-40, and IgE levels and compared these biomarkers with airway eosinophilia in asthmatic patients. We collected sputum, performed bronchoscopy, and matched peripheral blood samples from 67 asthmatic patients who remained symptomatic despite maximal inhaled corticosteroid treatment (mean FEV(1), 60% of predicted value; mean Asthma Control Questionnaire [ACQ] score, 2.7). Serum periostin levels are significantly increased in asthmatic patients with evidence of eosinophilic airway inflammation relative to those with minimal eosinophilic airway inflammation. A logistic regression model, including sex, age, body mass index, IgE levels, blood eosinophil numbers, Feno levels, and serum periostin levels, in 59 patients with severe asthma showed that, of these indices, the serum periostin level was the single best predictor of airway eosinophilia (P = .007). Periostin is a systemic biomarker of airway eosinophilia in asthmatic patients and has potential utility in patient selection for emerging asthma therapeutics targeting T(H)2 inflammation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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                Author and article information

                Contributors
                enoguchi@md.tsukuba.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                30 July 2018
                30 July 2018
                2018
                : 8
                : 11450
                Affiliations
                [1 ]ISNI 0000 0001 0692 8246, GRID grid.163577.1, Departments of Otorhinolaryngology Head & Neck Surgery, , Faculty of Medical Sciences, University of Fukui, ; Fukui, Japan
                [2 ]ISNI 0000 0001 2369 4728, GRID grid.20515.33, Department of Medical Genetics, , Faculty of Medicine, University of Tsukuba, ; Tsukuba, Japan
                [3 ]ISNI 0000 0001 1302 4472, GRID grid.261356.5, Department of Otolaryngology-Head and Neck Surgery, , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, ; Okayama, Japan
                [4 ]ISNI 0000 0004 0467 0255, GRID grid.415020.2, Department of Otolaryngology, , Jichi Medical University, Saitama Medical Center, ; Saitama, Japan
                [5 ]ISNI 0000 0001 0702 8004, GRID grid.255137.7, Department of Otorhinolaryngology Head & Neck Surgery, , Dokkyo Medical University, ; Tochigi, Japan
                [6 ]ISNI 0000 0004 0467 212X, GRID grid.413045.7, Department of Otorhinolaryngology, , Yokohama City University Medical Center, ; Kanagawa, Japan
                [7 ]ISNI 0000 0004 0531 3030, GRID grid.411731.1, Department of Otorhinolaryngology, , International University of Health and Welfare School of Medicine, ; Narita, Japan
                [8 ]ISNI 0000 0001 1172 4459, GRID grid.412339.e, Division of Medical Biochemistry, Department of Biomolecular Sciences, , Saga Medical School, ; Saga, Japan
                [9 ]ISNI 0000 0001 1172 4459, GRID grid.412339.e, Department of Laboratory Medicine, Department of Biomolecular Sciences, , Saga Medical School, ; Saga, Japan
                [10 ]Shino-test Co. Ltd., Sagamihara, Japan
                [11 ]ISNI 0000 0001 2151 536X, GRID grid.26999.3d, University Hospital Medical Information Network Research Center, University of Tokyo, ; Tokyo, Japan
                Article
                29612
                10.1038/s41598-018-29612-2
                6065353
                30061580
                f23415c8-becc-4a84-877d-8ed97e0a9f04
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 2 August 2017
                : 10 July 2018
                Funding
                Funded by: the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and development, AMED
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