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SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis
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 da...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411256/ https://www.ncbi.nlm.nih.gov/pubmed/32849763 http://dx.doi.org/10.3389/fgene.2020.00633 |
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author | Huang, Jin Gao, Hong Tan, Hong-Zhuan |
author_facet | Huang, Jin Gao, Hong Tan, Hong-Zhuan |
author_sort | Huang, Jin |
collection | PubMed |
description | 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+. |
format | Online Article Text |
id | pubmed-7411256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74112562020-08-25 SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis Huang, Jin Gao, Hong Tan, Hong-Zhuan Front Genet Genetics 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+. Frontiers Media S.A. 2020-07-31 /pmc/articles/PMC7411256/ /pubmed/32849763 http://dx.doi.org/10.3389/fgene.2020.00633 Text en Copyright © 2020 Huang, Gao and Tan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Huang, Jin Gao, Hong Tan, Hong-Zhuan SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title | SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title_full | SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title_fullStr | SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title_full_unstemmed | SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title_short | SOX1 Promoter Hypermethylation as a Potential Biomarker for High-Grade Squamous Intraepithelial Neoplasia Lesion and Cervical Carcinoma: A Meta-Analysis With Trial Sequential Analysis |
title_sort | sox1 promoter hypermethylation as a potential biomarker for high-grade squamous intraepithelial neoplasia lesion and cervical carcinoma: a meta-analysis with trial sequential analysis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411256/ https://www.ncbi.nlm.nih.gov/pubmed/32849763 http://dx.doi.org/10.3389/fgene.2020.00633 |
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