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. 2023 Apr 21;13(1):6592.
doi: 10.1038/s41598-023-32944-3.

Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps

Affiliations

Transcriptomics unravels molecular changes associated with cilia and COVID-19 in chronic rhinosinusitis with nasal polyps

Åsa Torinsson Naluai et al. Sci Rep. .

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common upper respiratory tract complication where the pathogenesis is largely unknown. Herein, we investigated the transcriptome profile in nasal mucosa biopsies of CRSwNP patients and healthy individuals. We further integrated the transcriptomics data with genes located in chromosomal regions containing genome-wide significant gene variants for COVID-19. Among the most significantly upregulated genes in polyp mucosa were CCL18, CLEC4G, CCL13 and SLC9A3. Pathways involving "Ciliated epithelial cells" were the most differentially expressed molecular pathways when polyp mucosa and non-polyp mucosa from the same patient was compared. Natural killer T-cell (NKT) and viral pathways were the most statistically significant pathways in the mucosa of CRSwNP patients compared with those of healthy control individuals. Upregulated genes in polyp mucosa, located within the genome-wide associated regions of COVID-19, included LZTFL1, CCR9, SLC6A20, IFNAR1, IFNAR2 and IL10RB. Interestingly, the second most over-expressed gene in our study, CLEC4G, has been shown to bind directly to SARS-CoV-2 spike's N-terminal domain and mediate its entry and infection. Our results on altered expression of genes related to cilia and viruses point to the de-regulation of viral defenses in CRSwNP patients, and may give clues to future intervention strategies.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Top 20 differentially expressed genes (DEGs) between non-polyp CRSwNP patient and control patient. (a) Polyp mucosa versus non-polyp (unaffected) mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp (unaffected) mucosa from CRSwNP patient. p-values are unadjusted and shown for the comparisons between non-polyp mucosa versus polyp mucosa and control patient mucosa. DESeq2 R package analysis, including sex and age as covariates.
Figure 1
Figure 1
Top 20 differentially expressed genes (DEGs) between non-polyp CRSwNP patient and control patient. (a) Polyp mucosa versus non-polyp (unaffected) mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp (unaffected) mucosa from CRSwNP patient. p-values are unadjusted and shown for the comparisons between non-polyp mucosa versus polyp mucosa and control patient mucosa. DESeq2 R package analysis, including sex and age as covariates.
Figure 2
Figure 2
Heatmap of the 40 most differentially expressed genes (DEGs). (a) Polyp mucosa versus non-polyp mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp mucosa from CRSwNP patient. DESeq2 R package analysis, including sex and age as covariates. Heatmaps were generated using “pheatmap” in R, R version 4.1.3.
Figure 2
Figure 2
Heatmap of the 40 most differentially expressed genes (DEGs). (a) Polyp mucosa versus non-polyp mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp mucosa from CRSwNP patient. DESeq2 R package analysis, including sex and age as covariates. Heatmaps were generated using “pheatmap” in R, R version 4.1.3.
Figure 3
Figure 3
Gene expression of all expressed genes. Vulcano plot showing the negative logarithm of the p-value on the y-axis and the fold change of all expressed genes from the comparison of (a) Polyp mucosa versus non-polyp mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp mucosa from CRSwNP patient. DESeq2 R package analysis, including sex and age as covariates.
Figure 3
Figure 3
Gene expression of all expressed genes. Vulcano plot showing the negative logarithm of the p-value on the y-axis and the fold change of all expressed genes from the comparison of (a) Polyp mucosa versus non-polyp mucosa from the same CRSwNP patient and (b) Healthy control patient mucosa versus non-polyp mucosa from CRSwNP patient. DESeq2 R package analysis, including sex and age as covariates.
Figure 4
Figure 4
Plot showing the principal components analysis (PCA) grouped by healthy control patient mucosa, non-polyp and polyp mucosa from CRSwNP patient.
Figure 5
Figure 5
Differentially expressed genes (DEGs) in chromosomal regions showing genome wide significant association with COVID-19. Four chromosomal regions were included, (a) chromosome 3, (b) chromosome 12, (c) chromosome 19 and (d) chromosome 21.
Figure 5
Figure 5
Differentially expressed genes (DEGs) in chromosomal regions showing genome wide significant association with COVID-19. Four chromosomal regions were included, (a) chromosome 3, (b) chromosome 12, (c) chromosome 19 and (d) chromosome 21.
Figure 5
Figure 5
Differentially expressed genes (DEGs) in chromosomal regions showing genome wide significant association with COVID-19. Four chromosomal regions were included, (a) chromosome 3, (b) chromosome 12, (c) chromosome 19 and (d) chromosome 21.

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