Abstract
Background: DNA methylation has been widely assessed as a potential biomarker for the early detection of cervical cancer (CC). Herein, we assessed the associations of SOX1 promoter hypermethylation with squamous intraepithelial lesion and CC.Methods: Published studies and genome-wide methylation datasets were searched from electronic databases (up to April 2019). The associations of SOX1 hypermethylation with high-grade squamous intraepithelial lesion (HSIL) and CC risks were evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). The summary receiver operator characteristic test was used to assess the diagnostic value of the SOX1 promoter hypermethylation of CC and intraepithelial neoplasia type III or worse (CIN3+). Trial sequential analysis (TSA) was performed to evaluate the stability of results and estimate the required information size (RIS).Results: In this meta-analysis of 17 published studies, the SOX1 methylation rates increased among low-grade SIL (LSIL, 27.27%), HSIL (40.75%), and CC (84.56%) specimens. Compared with control specimens, SOX1 promoter hypermethylation progressively increased the risk of HSIL by 4.20-fold (p < 0.001) and CC by 41.26-fold (p < 0.001). The pooled sensitivity of SOX1 methylation was estimated to be 0.85 (95% CI: 0.81–0.88) in differentiating patients with CC, corresponding to a specificity of 0.72 (95% CI: 0.69–0.75) and an area under the curve (AUC) of 0.93. Furthermore, the pooled sensitivity of SOX1 methylation was estimated to be 0.75 (95% CI: 0.72–0.78) in differentiating patients with CIN3+, corresponding to a specificity of 0.71 (95% CI: 0.69–0.73) and an AUC of 0.84. The pooled results of TCGA and GEO datasets showed that all CpG sites in SOX1 were associated with CC and 16 of 19 CpG sites were associated with HSIL. The results of TSA illustrated that the size was sufficient and significant associations were observed.Conclusion: This meta-analysis indicated that SOX1 promoter hypermethylation might have a potential value in the clinical diagnosis of CC and CIN3+.
Highlights
Cervical cancer (CC), a common gynecological malignant tumor, is a major disease that seriously threatens women’s health (Wright et al, 2019)
Our analysis showed that SOX1 hypermethylation could be a useful biomarker for CIN3+ (DOR = 8.62, 95% confidence intervals (CIs): 6.00–12.37)
SOX1 methylation is associated with liver cancer, and SOX1 promoter methylation level is significantly higher in patients with high TNM stage than in those with low TNM stage
Summary
Cervical cancer (CC), a common gynecological malignant tumor, is a major disease that seriously threatens women’s health (Wright et al, 2019). According to 2018 global cancer statistics, CC is the fourth leading cause of cancer death with 569,847 new cases and 311,365 deaths per year (Bray et al, 2018). More than 80% of these cases occur in developing countries, in which CC is the leading cause of cancer deaths (Di et al, 2015). The development of CC is characterized as a progressive process from normal epithelium to squamous intraepithelial lesion (SIL) and eventually to invasive carcinoma. According to the categorization of the 2001 Bethesda System, the diagnosis of LSIL including productive HPV infection, CIN1 and mild dysplasia, while the category of HSIL including CIN 2 or 3, moderate and extensive dysplasia and carcinoma in situ (CIS) (Solomon et al, 2002). We assessed the associations of SOX1 promoter hypermethylation with squamous intraepithelial lesion and CC
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