Gene network approach reveals co-expression patterns in nasal and bronchial epithelium

Kai Imkamp,Peter Horvatovich,Victor Bernal,Cornelis J Vermeulen,Maarten Van Den Berge,Huib A M Kerstjens,Alen Faiz,Marco Grzegorzcyk,Irene H Heijink,Victor Guryev

doi:10.1038/s41598-019-50963-x

Abstract

Nasal gene expression profiling is a new approach to investigate the airway epithelium as a biomarker to study the activity and treatment responses of obstructive pulmonary diseases. We investigated to what extent gene expression profiling of nasal brushings is similar to that of bronchial brushings. We performed genome wide gene expression profiling on matched nasal and bronchial epithelial brushes from 77 respiratory healthy individuals. To investigate differences and similarities among regulatory modules, network analysis was performed on correlated, differentially expressed and smoking-related genes using Gaussian Graphical Models. Between nasal and bronchial brushes, 619 genes were correlated and 1692 genes were differentially expressed (false discovery rate <0.05, |Fold-change|>2). Network analysis of correlated genes showed pro-inflammatory pathways to be similar between the two locations. Focusing on smoking-related genes, cytochrome-P450 pathway related genes were found to be similar, supporting the concept of a detoxifying response to tobacco exposure throughout the airways. In contrast, cilia-related pathways were decreased in nasal compared to bronchial brushes when focusing on differentially expressed genes. Collectively, while there are substantial differences in gene expression between nasal and bronchial brushes, we also found similarities, especially in the response to the external factors such as smoking.

Highlights

Nasal gene expression profiling is a new approach to investigate the airway epithelium as a biomarker to study the activity and treatment responses of obstructive pulmonary diseases
We found that genes correlated between the two locations have both higher mean expression and greater variation than non-correlated genes (Fig. 1B,C), indicating that variation of gene expression is required for correlation
We found no difference with respect to the nasal-bronchial relation between samples from the nose and bronchus when looking at all genes, while for the 619 correlated genes (CO), the intra-patient nasal bronchial correlations were more correlated than across patients (Fig. 2A–C)

Summary

Introduction

Nasal gene expression profiling is a new approach to investigate the airway epithelium as a biomarker to study the activity and treatment responses of obstructive pulmonary diseases. We identified a bronchial gene expression signature that is associated with COPD alteration and disease severity with similar gene expression changes in lung tissue affected by COPD5. We previously demonstrated that the nasal epithelium can be used to detect changes in COPD-associated gene expression and showed that the nasal epithelial COPD related gene expression signature partly overlaps with COPD-associated bronchial epithelial gene expression[9]. This strengthens the hypothesis that the upper and lower airways have a common COPD-related gene expression profile, the united ‘airway field of injury’. The easy availability to nasal epithelium, nasal gene expression provides the opportunity to assess disease-related phenotypes and determine treatment outcome

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