Abstract
BACKGROUND: The correlation between methylation of paired box gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) with human papillomavirus (HPV) infection and the progression of cervical lesions is not well understood. This study aims to explore the potential value of PAX1 and SOX1 as diagnostic biomarkers for cervical diseases. METHODS: A total of 139 cervical biopsy tissue samples were obtained from the Department of Pathology, the Seventh Medical Center, Chinese PLA General Hospital from 2021 to 2023. The samples include 32 cases of chronic cervicitis (inflammation group), 30 cases of low-grade squamous intraepithelial lesions (LSIL group), 50 cases of high-grade squamous intraepithelial lesions (HSIL group), and 27 cases of cervical squamous cell carcinoma (CSCC group). DNA was extracted from paraffin-embedded tissues, and the levels of HPV infection and methylation of PAX1 and SOX1 were detected. RESULTS: The methylation index (M-index) of PAX1 and SOX1 in the HSIL and CSCC groups is significantly higher than in the inflammation group (both P < 0.0001), with no significant difference between the LSIL and inflammation groups. There is no significant difference in the positive PAX1 and SOX1 methylation rate with HPV infection and age. The positive rates of PAX1 methylation in the inflammation, LSIL, HSIL, and CSCC groups were 3.13%, 10.00%, 44.00%, and 88.89%, respectively. The positive rates of SOX1 methylation were 3.13%, 10.00%, 40.00%, and 77.78%, respectively, and increasing with the progression of cervical lesions (R(2) = 0.9189/R(2) = 0.9279, P < 0.0001/P < 0.0001). Comparing LSIL, HSIL, and CSCC with the inflammation group and using cervical biopsy pathology diagnosis as the gold standard, methylation of PAX1 and SOX1 is a risk factor for HSIL and CSCC, with odds ratio (OR) values significantly increasing as lesions progress. The sensitivity of PAX1 and SOX1 methylation to cervical lesions increases with the progression of the lesions. CONCLUSIONS: Methylation of SOX1 and PAX1 is not associated with HPV infection. The positive rate of methylation for SOX1 and PAX1 is positively correlated with cervical lesions, which can serve as potential biomarkers for HSIL and CSCC. They are risk factors and potential screening indicators for HSIL and above cervical lesions.