CRS is an otolaryngology disease with a high recurrence rate. According to the absence or existence of nasal polyps (NPs), they can be classified into CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP). Pyroptosis is a kind of programmed cell death, which is closely related to the inflammatory reaction of many diseases. In this paper, the role of pyroptosis -related genes in CRS was discussed, but it was not clear. Therefore, this paper analyzed the different expressions of the training set data after batch correction. The DEGs were imported into the WGCNA package for analysis, and the gene module related to CRS was screened. Then the genes in the gene module were intersected with PRGs collected in previous literature. GO and KEGG enrichment analyses were performed on the intersecting genes (Fig. 5).In the GO enrichment pathway, we determined that pyroptosis had closed relatedness to infection [6]. IL-17A can induce the focal death of human nasal epithelial cells (hNEC) in patients with CRSwNP through extracellular signal-regulated kinase (ERK) pathway [7]. NLRP3 is closely related to inflammation, and it has been confirmed that NLRP3 is involved in the pathogenesis of CRS [8]. S100A8 is a calcium and zinc binding protein that plays an important role in regulating inflammatory processes and immune response. Nakatani A et al. confirmed that S100A8 could induce the production of interleukin − 1β in the nasal epithelium, which is involved in the pathogenesis of eosinophilic rhinosinusitis [9]. In the KEGG enrichment pathway, Ding S et al. certained that the NOD-like receptor signaling pathway is a critical CRS signaling pathway through network pharmacological analysis [10]. There are differences in the expression of key apoptosis markers at mRNA and miRNA levels in patients with CSRwNP [11]. Apigenin can alleviate the nasal mucosa remodeling induced by TGF-β1 by inhibiting the MAPK/NF-kB signaling pathway of CRS, which indicates that apigenin can be used as a potential therapeutic drug for CRS [12].
In addition, we analyzed the PPI network of intersection genes and screened the hub genes (CASP3, IL18, NAIP, NLRC4, and TP53) by using three algorithms in cytoscape. The protein encoded by CASP3 gene is a cysteine-aspartic protease, which is involved in the signal pathway of apoptosis and inflammation. The two pathways are all associated with CRS [8][11]. CRS is characterized by persistent symptomatic inflammation of nasal and sinus mucosa [13]. IL-9 plays an important role in triggering an inflammatory reaction, stimulating cell proliferation, and preventing cell apoptosis by binding with the IL-9 receptor (IL-9R). They are overexpressed at protein and mRNA levels in CRS [14]. IL-18 has been proven to be a potential therapeutic target for CRS [15]. The protein encoded by NAIP gene can inhibit cell apoptosis induced by various signals. Specifically, it is an anti-apoptosis protein that inhibits the activities of CASP3, CASP7, and CASP9. NLRC4 encodes a member of the NLR family containing a caspase recruitment domain and is also a key component of inflammatory corpuscles [16]. TP53 can induce cell cycle arrest, apoptosis, aging, DNA repair, or metabolic changes. Huang GJ et al. identified TP53 as an important DEFGs of CRSwNP [17].
We also verified the ROC curves of the hub genes. The AUC of these genes in the training set and the test set was greater than 0.5, which was of diagnostic significance for CRS. Based on the expression of hub genes, we evaluated the infiltration abundance of 22 kinds of immune cells in CRS and its control group. Among them, the infiltration abundance of Plasma cells, T cells follicular helper, Macrophages M2, Dendritic cells activated, and Neutrophils cells in the two groups were significantly different. The relationship between these immune cells and CRS can be confirmed in the following literature. Arjun Mandih et al. used CD27 as a marker of plasma cells and confirmed through experiments that the existence of biofilm in CRS seems to be related to the host inflammatory reaction caused by plasma cells [18]. T cells follicular helper and their effector cytokine IL-21 play an essential role in the occurrence and development of CRSwNP [19]. M2 macrophage has an anti-inflammatory effect. Loss of SENP3 will increase the number of M2 macrophages in the nasal mucosa, which is of great significance to CRS [20]. Studying the expression of different dendritic cells (DC) in patients with CRSwNP can be used as a critical measure in the progress of the disease [21]. Neutrophils have also been confirmed to be closely related to CRS pathology [22].
Finally, the interaction network between the hub genes and miRNA was constructed. So was the hub genes and TF. MiRNA can be used as a potential negative regulator of inflammation [23]. In the mouse experiment of CRS, Gu X et al. confirmed that the expression of mir-335-5p (the miRNA linked with NAIP and NLRC4) was related to CRS [24]. Morawska-Kochman M et al. found that there was no significant difference in the level of mir-146a-5p (miRNA linked with IL-18, NAIP, and NLRC4) between HC and CRSwNP, which may be due to the delayed induction of miR-146a/b, which may be a compensatory response to inhibit inflammation [11][25]. In Fig. 10B, we found that the protein encoded by MEF2A gene was involved in apoptosis. Previous studies have confirmed that apoptosis plays a vital role in the pathogenesis of CRS [11]. NR3C1 is involved in inflammatory reactions. Refractory rhinosinusitis (DTRS) is a particular type of CRS. Wu C et al. indicated that NR3C1 gene polymorphism is significantly related to DTRS [26]. EGR1 can regulate cell survival, proliferation, and cell death, activate the expression of p53/TP53 and TGFB1, and regulate the expression of a protein involved in the inflammatory process and tissue injury after ischemia, such as CXCL2 and IL1B. The level of CXCL2 is significantly correlated with the scope of CRSsNP disease [27]. Mfuna Endam L et al. studied the association between single nucleotide polymorphisms (SNP) in IL1B (rs16944) gene in CRS patients. Unfortunately, the association with IL1B has not been found, and further research is needed in the future [28].