Secreted phosphoprotein 1 is associated with epithelial cell proliferation and PI3K/AKT signalling in sinonasal inverted papilloma

<h4>Objectives</h4>Sinonasal inverted papilloma is a locally aggressive epithelial lesion with a relatively high recurrence rate, yet the molecular basis of its proliferative behaviour remains incompletely understood. This study investigated the clinical relevance of secreted phosphoprotein 1 in sinonasal inverted papilloma and its association with epithelial cell proliferation and related signalling pathways.<h4>Methods</h4>Differentially expressed genes were identified from the GSE193016 dataset, followed by gene set enrichment analysis. The expression of secreted phosphoprotein 1 and the cell cycle-related molecules cell division cycle 25C and cyclin A2 in clinical specimens was assessed using quantitative PCR, Western blotting, and immunohistochemistry. Associations between secreted phosphoprotein 1 expression and postoperative recurrence were assessed based on follow-up data. In vitro experiments using human nasal epithelial cells were conducted to examine the effects of altered secreted phosphoprotein 1 expression on cell proliferation-associated phenotypes, and pathway inhibition assays were performed to investigate the involvement of the PI3K/AKT signalling pathway.<h4>Results</h4>Secreted phosphoprotein 1 expression was significantly upregulated in sinonasal inverted papilloma tissues, with higher levels observed in advanced-stage cases (T3-T4), and was associated with postoperative recurrence. The expression of the cell cycle-related molecules cell division cycle 25C and cyclin A2, positively correlated with secreted phosphoprotein 1 expression and increased with disease progression. In vitro epithelial cell models demonstrated that modulation of secreted phosphoprotein 1 expression was accompanied by corresponding changes in cellular proliferative capacity and cell cycle-related protein expression. Pathway inhibition assays further suggested that PI3K/AKT signalling may be involved in secreted phosphoprotein 1-associated alterations in cell cycle regulation.<h4>Conclusion</h4>These findings indicate that secreted phosphoprotein 1 is highly expressed in sinonasal inverted papilloma and may be associated with epithelial cell proliferation and PI3K/AKT signalling. In addition, secreted phosphoprotein 1 expression correlates with disease recurrence, highlighting its potential research value as a biological marker, while the underlying mechanisms warrant further investigation.