Li Dan-Yang, Wang Lin, Zhang Ji-Sheng, Zi Jia-Jia, Chen Han, Dong Zi-Hui, Yu Long-Gang, Jiang Yan
Department of Otorhinolaryngology Head and Neck Surgery The Affiliated Hospital of Qingdao University Qingdao China.
World J Otorhinolaryngol Head Neck Surg. 2024 Sep 4;11(2):281-289. doi: 10.1002/wjo2.213. eCollection 2025 Jun.
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.
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.
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.
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.
鼻窦内翻性乳头状瘤（SNIP）是一种良性肿瘤类型，因其具有恶变潜能而受到越来越多的研究关注。然而，迄今为止尚无关于SNIP中铁死亡或相关蛋白的研究。因此，本研究旨在探讨SNIP发病机制与铁死亡活性相关蛋白（包括p53、SAT1和ALOX15）表达之间的相关性。
收集44例SNIP患者的样本，并从28例鼻中隔偏曲患者中获取对照中鼻甲样本。通过定量实时PCR（qRT-PCR）、蛋白质免疫印迹分析（WB）和免疫组织化学（IHC）比较这些样本中p53、SAT1和ALOX15的RNA和蛋白质水平。通过查询GSE193016数据集进一步验证mRNA的表达。还评估了这三个基因表达水平之间的相关性。然后，使用Krouse分期系统对这些患者进行分级，并探讨疾病不同阶段p53、SAT1和ALOX15表达的差异。最后，通过qRT-PCR和IHC比较这些基因在乳头状瘤和鳞状细胞癌中的表达差异。
SNIP样本中p53、SAT1和ALOX15的mRNA和蛋白质水平显著高于对照样本，并且观察到这三种蛋白质水平之间存在强相关性。此外，在SNIP中，T4期的p53、SAT1和ALOX15表达水平显著高于T2期。与内翻性乳头状瘤相比，鳞状细胞癌中p53和SAT1显著升高。然而，鳞状细胞癌中ALOX15的表达趋于降低。
这些结果支持p53/SAT1/ALOX15铁死亡途径蛋白在SNIP发病机制中可能发挥作用，尽管未来基于分子生物学的研究对于验证这一假设至关重要。
