An Integrated Machine Learning Framework for Developing and Validating a Diagnostic Model of Hub Genes Related to Lipid Metabolism in Chronic Rhinosinusitis.

PURPOSE

The study aimed to identify key genes related to lipid metabolism in chronic sinusitis and understand their biological implications, considering the growing interest in the association between chronic sinusitis - a complex inflammatory condition - and lipid metabolism due to lipids' role in inflammation and immunity.

METHODS

Gene expression data from bulk - RNA sequence was analyzed and intersected with lipid metabolism genes and WGCNA module genes from the MSigDB database. Immune infiltration analysis was conducted. Machine learning techniques were used to develop a diagnostic model. qRT - PCR and immunofluorescence techniques were employed to confirm gene involvement. Potential targeted drugs were identified through relevant analyses.

RESULTS

41 hub genes were identified, which were involved in pathways like G protein - coupled receptor signaling, TGF - beta receptor signaling, and responses to oxidative stress and nitrogen compounds. Enrichment analyses suggested links to ubiquitin - mediated proteolysis, mTOR signaling, and MAPK signaling. A significant presence of immune cells was detected in the chronic sinusitis group. A combined RF+Stepglm model was developed, comprising six genes (KPNA3, RAB35, GLE1, RNF139, OSMR, and PDPK1), which demonstrated good diagnostic performance (AUC = 0.848). Potential targeted drugs such as Raloxifene and Hesperidin were identified. qRT - PCR and immunofluorescence confirmed that the expression levels of RAB35, GLE1, and OSMR were significantly higher in CRS samples compared to normal ones.

CONCLUSION

This research highlights the role of lipid metabolism in chronic sinusitis and provides a basis for the development of targeted therapies.