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Phosphoinositide 3-kinase-delta could be a biomarker for eosinophilic nasal polyps.

ABSTRACT: Nasal polyps (NP) cause diverse clinical symptoms of chronic rhinosinusitis (CRS). Chronic inflammation of sinonasal mucosa is known to be crucial in NP formation. We aimed to define the implications of phosphoinositide 3-kinase (PI3K)-δ in nasal inflammation associated with NP by analyzing NP tissue obtained from CRS patients. Results showed that expression of p110δ, a regulatory subunit of PI3K-δ, in NP tissue was increased compared to control tissue. Increased p110δ expression was closely correlated with more severe CRS features. Interestingly, p110δ expression was increased in eosinophilic NP, which are closely related to more complicated clinical courses of the disease. Furthermore, CRS patients possessing NP with higher p110δ expression displayed more eosinophils in NP tissue and blood, higher levels of IL-5 in NP tissue, and more severe features of the disease. Therefore, PI3K-δ may contribute to the formation of NP, especially eosinophilic NP associated with more severe clinical presentations and radiological features.

SUBMITTER: Kim JS

PROVIDER: S-EPMC6207677 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Phosphoinositide 3-kinase-delta could be a biomarker for eosinophilic nasal polyps.

Kim Jong Seung JS Jeong Jae Seok JS Lee Kyung Bae KB Kim So Ri SR Choe Yeong Hun YH Kwon Sam Hyun SH Cho Seong Ho SH Lee Yong Chul YC

Scientific reports 20181030 1

Nasal polyps (NP) cause diverse clinical symptoms of chronic rhinosinusitis (CRS). Chronic inflammation of sinonasal mucosa is known to be crucial in NP formation. We aimed to define the implications of phosphoinositide 3-kinase (PI3K)-δ in nasal inflammation associated with NP by analyzing NP tissue obtained from CRS patients. Results showed that expression of p110δ, a regulatory subunit of PI3K-δ, in NP tissue was increased compared to control tissue. Increased p110δ expression was closely cor ...[more]

PMID: 30375439

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Project description:BackgroundIndividuals with eosinophilic chronic rhinosinusitis with nasal polyps(eCRSwNP) exhibited worse outcomes and higher postoperative recurrence rates. This study aimed to identify biomarkers that can aid in the early differentiation of eCRSwNP and enhance our comprehension of its pathophysiology.MethodsWe recruited two independent cohorts. In the discovery cohort, CRSwNP was categorized into eCRSwNP and non-eosinophilic CRSwNP(neCRSwNP), and serum proteomics was performed to identify differentially expressed proteins between the two groups. These candidate proteins were chosen and confirmed in the validation cohort using an enzyme-linked immunosorbent assay (ELISA), Western blot (WB), quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescence (IF), and their predictive values and associations with tissue eosinophilic pathophysiology were evaluated.ResultsWe identified a total of 39 differential proteins between the two groups, including 20 proteins upregulated and 19 downregulated in the eCRSwNP group. Further validation was conducted on the top 5 proteins that were up or down-regulated. Results from the ELISA showed that levels of serum MRC1, CDH13, and MMP2 were significantly higher, TRIM28 was lower in the eCRSwNP group compared to the neCRSwNP group (all P<0.05), and serum MRC1 (AUC=0.742, P<0.001) and MMP2 (AUC=0.766, P<0.001) levels exhibited promising predicting values for eCRSwNP. Moreover, qRT-PCR and WB analysis found that MMP2 and MRC1 expressions were enhanced in the eCRSwNP group compared to the neCRSwNP group (all P<0.01), and their levels were positively correlated with the number and percentages of tissue eosinophils (all P<0.01). The IF suggested that MMP2 and MRC1 were overexpressed in the nasal polyps tissues of eCRSwNP patients, and MMP2 was mainly located on eosinophils.ConclusionCirculating proteins identified by proteomics could serve as potential preoperative biomarkers for distinguishing eCRSwNP. Among them, MMP2 was enhanced in eCRSwNP and correlated with tissue eosinophilia, which provided valuable insights into the pathophysiology of eCRSwNP.

Project description:BackgroundRecent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.MethodsPatients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).ResultsMicroarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1alpha, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated.ConclusionThis study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.

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Phosphoinositide 3-kinase-delta could be a biomarker for eosinophilic nasal polyps.

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Phosphoinositide 3-kinase-delta could be a biomarker for eosinophilic nasal polyps.

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