Expression and clinical significance of the p53/SAT1/ALOX15 ferroptosis-associated proteins in sinonasal inverted papilloma.

Abstract

Objectives: Sinonasal inverted papilloma (SNIP) is a benign tumor type that has been subject to growing levels of research interest owing to its potential for malignant transformation. However, there have been no studies to date of ferroptosis or related proteins in SNIP. Accordingly, this study was designed to examine correlative relationships between SNIP pathogenesis and the expression of proteins associated with ferroptotic activity, including p53, SAT1, and ALOX15.

Methods: Samples were collected from 44 total SNIP patients, and control middle turbinate samples were obtained from 28 patients with deviated septums. The RNA and protein levels of p53, SAT1, and ALOX15 were compared between these samples via quantitative real-time PCR (qRT-PCR), Western blot analysis (WB), and immunohistochemistry (IHC). The expression of mRNA was further validated by interrogating the GSE193016 data set. The correlations among the expression levels of these three genes were also assessed. Then, the Krouse stage system was used to grade these patients and to explore differences in p53, SAT1, and ALOX15 expression among different stages of the disease. Lastly, we compared the differences in the expression of these genes in inverted papilloma and squamous cell carcinoma by qRT-PCR and IHC.

Results: SNIP samples exhibited significantly higher p53, SAT1, and ALOX15 mRNA and protein levels than control samples, and strong correlations were observed between the levels of these three proteins. Furthermore, the expression levels of p53, SAT1, and ALOX15 were significantly higher in stage T4 compared to T2 in SNIP. p53 and SAT1 were significantly elevated in squamous carcinomas compared to inverted papilloma. However, the expression of ALOX15 tended to decrease in squamous carcinoma.

Conclusion: These results support a potential role for the p53/SAT1/ALOX15 ferroptotic pathway proteins in SNIP pathogenesis, although future molecular biology-based studies will be essential to test this hypothesis.