Identification of Potential Differentially Methylated Gene-Related Biomarkers in Endometriosis

Abstract

Aim: To identify epigenetic alterations of differentially expressed genes and screen out targeted therapeutic drugs in endometriosis. Methods: Based on the Gene Expression Omnibus database and a series of biological information analysis tools, supplemented by validation of clinical samples, aberrant DNA methylation-driven genes and their functions were explored, as well as possible targeted drugs. Results: This study screened out a range of DNA methylation-driven genes that were associated with powerful properties and corresponding pathways. Among them, BDNF and CCL2 were key genes in the development of endometriosis. Four chemical agents have been flagged as potential treatments for endometriosis. Conclusion: These candidate genes and small-molecule agents may be further explored as potential targets and drugs for endometriosis diagnosis and therapy, respectively.

Plain language summary

What is the significance of studying endometriosis? Endometriosis is a common gynecological benign disease affecting an estimated 5–10% of women in their reproductive years. Women with endometriosis suffer from chronic pelvic pain, dyspareunia and dysmenorrhea, and some patients face the possibility of infertility. What were the results of this study? The authors explored a number of key genes that may contribute to the etiology and pathogenesis of endometriosis, discussed the reasons for the changes in the expression levels of these hub genes and then screened for a number of effective small-molecule chemical drugs that may act on endometriosis. What do the results of this study mean? The authors carried out research from the three aspects of etiology, diagnosis and treatment of endometriosis. First, it demonstrated that endometriosis patients did have some differentially expressed genes compared with controls, and then in the analysis of these abnormally expressed genes, it was found that DNA methylation may play an essential role. This is a more meaningful hint, whether the occurrence of endometriosis can be suppressed by targeting methylation modification and then affecting the expression of key genes. In addition, the different severity of endometriosis will also have varying degrees of impact on patients’ quality of life. These results are also a good indicator of the severity of endometriosis. Therefore, early detection and timely treatment are guidelines for the treatment of endometriosis. Finally, some of the chemical agents identified to target the cause of endometriosis are expected to become new treatments for endometriosis, supported by the results of follow-up studies, which will lead to more accurate treatments for patients with fewer side effects than existing treatments.

Keywords::

• differentially expressed genes
• differentially methylated genes
• endometriosis
• miRNA–mRNA network
• severity

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2022-0249

Author contributions

GM Zhang designed and directed all the research. JX Li and YN He conducted the data processing and experimental analysis. T Liang, J Wang and XY Jiang drafted the manuscript. All authors reviewed and approved the final version of the manuscript.

Acknowledgments

The authors would like to thank the staff members of the Gene Expression Omnibus database and the Turku Endometriosis Database, as well as all the authors for making their valuable research data public.

Financial & competing interests disclosure

This study was supported by the National Natural Science Foundation of China (grant no. 81971359), the Natural Science Foundation of Heilongjiang Province (grant no. LH2019H027), the Heilongjiang Postdoctoral Program Foundation (LBH-Z19085) and the Outstanding Young Medical Talents Training Fund project of the First Affiliated Hospital of Harbin Medical University (HYD2020YQ0021). All clinical samples were obtained with informed consent and approved by the Ethics Commission of Harbin Medical University (202105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (grant no. 81971359), the Natural Science Foundation of Heilongjiang Province (grant no. LH2019H027), the Heilongjiang Postdoctoral Program Foundation (LBH-Z19085) and the Outstanding Young Medical Talents Training Fund project of the First Affiliated Hospital of Harbin Medical University (HYD2020YQ0021). All clinical samples were obtained with informed consent and approved by the Ethics Commission of Harbin Medical University (202105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.