Transcriptomic Analysis of Genes Associated with Oxidative Stress in Chronic Rhinosinusitis Patients with Nasal Polyps: Identifying Novel Genes Involved in Nasal Polyposis

Yih-Jeng Tsai; Yu-Ting Hsu; Ming-Chieh Ma; Chun-Kuang Wu; Sheng-Dean Luo; Wen-Bin Wu

doi:10.3390/antiox11101899

Transcriptomic Analysis of Genes Associated with Oxidative Stress in Chronic Rhinosinusitis Patients with Nasal Polyps: Identifying Novel Genes Involved in Nasal Polyposis

Antioxidants (Basel). 2022 Sep 25;11(10):1899. doi: 10.3390/antiox11101899.

Authors

Yih-Jeng Tsai^{1

2}, Yu-Ting Hsu³, Ming-Chieh Ma², Chun-Kuang Wu⁴, Sheng-Dean Luo^{5

6}, Wen-Bin Wu^{2

7}

Affiliations

¹ Department of Otolaryngology Head and Neck Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111045, Taiwan.
² School of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan.
³ Department of Otolaryngology Head and Neck Surgery, Cheng-Ching Hospital, Chung Kang Branch, Taichung 407211, Taiwan.
⁴ Department of Finance and International Business, College of Management, Fu Jen Catholic University, New Taipei City 242062, Taiwan.
⁵ Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833253, Taiwan.
⁶ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
⁷ Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City 242062, Taiwan.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress-which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)-were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.

Keywords: CRS; CRSwNP; ROS; lactoperoxidase; oxidative stress; transcriptional profiling.

Abstract

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