Autoimmune Disease-Related Hub Genes are Potential Biomarkers and Associated with Immune Microenvironment in Endometriosis

Yin-Ting Yang; Xi-Ya Jiang; Hong-Liang Xu; Guo Chen; Sen-Lin Wang; He-Ping Zhang; Lin Hong; Qin-Qin Jin; Hui Yao; Wei-Yu Zhang; Yu-Ting Zhu; Jie Mei; Lu Tian; Jie Ying; Jing-Jing Hu; Shu-Guang Zhou

doi:10.2147/IJGM.S417430

Autoimmune Disease-Related Hub Genes are Potential Biomarkers and Associated with Immune Microenvironment in Endometriosis

Int J Gen Med. 2023 Jul 10:16:2897-2921. doi: 10.2147/IJGM.S417430. eCollection 2023.

Authors

Yin-Ting Yang^#^{1

2}, Xi-Ya Jiang^#^{1

2}, Hong-Liang Xu^#³, Guo Chen^#^{1

2}, Sen-Lin Wang⁴, He-Ping Zhang³, Lin Hong^{1

2}, Qin-Qin Jin^{1

2}, Hui Yao^{1

2}, Wei-Yu Zhang^{1

2}, Yu-Ting Zhu^{1

2}, Jie Mei^{1

2}, Lu Tian^{1

2}, Jie Ying^{1

2}, Jing-Jing Hu⁵, Shu-Guang Zhou^{1

2}

Affiliations

¹ Department of Gynecology and Obstetrics, Maternity and Child Healthcare Hospital Affiliated to Anhui Medical University, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People's Republic of China.
² Department of Gynecology and Obstetrics, The Fifth Clinical College of Anhui Medical University, Hefei, Anhui, 230032, People's Republic of China.
³ Department of Pathology, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People's Republic of China.
⁴ Department of Medical Genetics Center, Anhui Province Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People's Republic of China.
⁵ Department of Gynecology and Obstetrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.

^# Contributed equally.

Abstract

Background: Endometriosis, a common gynecological condition, can cause symptoms such as dysmenorrhea, infertility, and abnormal bleeding, which can negatively affect a woman's quality of life. In the current study, the pathophysiological mechanisms of endometriosis are unknown, but this study suggests that endometriosis is associated with dysregulation of the autoimmune system. This study identify hub genes involved in the prevalence, identification and diagnostic value of endometriosis and autoimmune diseases, and explore the central genes and immune infiltrates, the diagnosis of endometriosis provides a new sight of thinking about diagnosis and treatment.

Methods and results: The relevant datasets for endometriosis GSE141549, GSE7305 and autoimmune disease-related genes (AIDGs) were downloaded from online database. Using the "limma" package and WGCNA to screen out the autoimmune disease related genes and endometriosis related genes, the autoimmune disease gene-related differential genes (AID-DEGs) progressive GO, KEGG enrichment analysis, and then using the protein interaction network and Cytoscape software to select hub genes (CXCL12, PECAM1, NGF, CTGF, WNT5A), using the "pROC" package to analyze the hub genes for the diagnostic value of endometriosis. The difference in the importance of hub genes for the diagnosis of endometriosis was analyzed by machine learning random forest, and the combined diagnostic value of hub genes was analyzed by using the Support Vector Machine (SVM) algorithm. The eutopic (EU) and ectopic endometrium (EC) immune microenvironment of endometriosis was evaluated using CIBERSORT, the correlation of hub genes to the immune microenvironment was analyzed.

Conclusion: The hub genes associated with AIDGs are differentially expressed in EC and EU of endometriosis and possess important value for the diagnosis of endometriosis. The hub genes have a very important impact on the immune microenvironment of endometriosis, which is important for exploring the connection between endometriosis and autoimmune diseases and provides a new insight for the subsequent study of immunotherapy and diagnosis of endometriosis.

Keywords: EMT; diagnosis; hub genes; immune microenvironment; immunotherapy.

Grants and funding

The Natural Science Foundation of Higher Education Institutions of Anhui Province (Grant No. KJ2021A0352, Grant No. YJS20230095), the Research Fund Project of Anhui Medical University (Grant No. 2020xkj236), and the Applied Medicine Research Project of Hefei Health Commission all provided funding in support of this work.