Wei Wei, Hu Xingyan, Han Qing
Department of Gynaecology, Yichang Central People's Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, People's Republic of China.
Cancer Manag Res. 2025 May 24;17:1005-1013. doi: 10.2147/CMAR.S513226. eCollection 2025.
This study aims to explore the value of Nuclear Transcription Factor Erythroid 2-Related Factor 2 (Nrf2) and the selective autophagy adapter protein p62/Sequestosome 1 (SQSTM1) in diagnosing cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SIL).
Paraffin specimens from 125 cervical SCC patients, 102 low-grade SIL (LSIL) patients, 101 high-grade SIL (HSIL) patients, and 49 patients with benign/reactive cervical squamous epithelium were collected at Yichang Central People's Hospital from 2010 to 2023. Immunohistochemistry was used to detect Nrf2 and p62 expression. Positive expression was defined by visible light yellow, brownish-yellow, or brown cytoplasmic particles. The correlation between the two proteins and their diagnostic value were analyzed.
Both Nrf2 and p62 were predominantly localized to the cytoplasm in various cervical lesions. The expression levels of Nrf2 and p62 were significantly higher in LSIL, HSIL, and SCC than in benign/reactive epithelium (all <0.001), and lower in LSIL than in HSIL and SCC (all <0.001). A positive correlation was found between Nrf2 and p62 in all lesion types (all <0.05). ROC analysis indicated that the diagnostic accuracy was enhanced when Nrf2 and p62 were used in combination, as opposed to using either marker individually.
Nrf2 and p62 are either not expressed or expressed at low levels in benign/reactive squamous epithelium, with expression increasing in LSIL, and being highest in HSIL and SCC. Both markers show a positive correlation across different cervical lesions, and either Nrf2 or p62 alone can effectively diagnose various cervical lesions, with even better diagnostic outcomes when used in combination.
本研究旨在探讨核转录因子红系2相关因子2（Nrf2）和选择性自噬衔接蛋白p62/聚集体蛋白1（SQSTM1）在诊断宫颈鳞状细胞癌（SCC）和鳞状上皮内病变（SIL）中的价值。
收集2010年至2023年在宜昌市中心人民医院就诊的125例宫颈SCC患者、102例低级别SIL（LSIL）患者、101例高级别SIL（HSIL）患者以及49例宫颈鳞状上皮良性/反应性病变患者的石蜡标本。采用免疫组织化学法检测Nrf2和p62的表达。阳性表达以可见光下淡黄色、棕黄色或棕色细胞质颗粒为判断标准。分析两种蛋白之间的相关性及其诊断价值。
在各种宫颈病变中，Nrf2和p62主要定位于细胞质。Nrf2和p62在LSIL、HSIL和SCC中的表达水平显著高于良性/反应性上皮（均<0.001），且在LSIL中的表达低于HSIL和SCC（均<0.001）。在所有病变类型中，Nrf2和p62之间均呈正相关（均<0.05）。受试者工作特征（ROC）分析表明，与单独使用任一标志物相比，联合使用Nrf2和p62可提高诊断准确性。
Nrf2和p62在良性/反应性鳞状上皮中不表达或低表达，在LSIL中表达增加，在HSIL和SCC中表达最高。两种标志物在不同宫颈病变中均呈正相关，单独使用Nrf2或p62均可有效诊断各种宫颈病变，联合使用时诊断效果更佳。
