Identification of immune- and autophagy-related genes and effective diagnostic biomarkers in endometriosis: a bioinformatics analysis

Abstract

Background: To identify autophagy-and immune-related hub genes affecting the diagnosis and treatment of endometriosis.Methods: Gene expression data were downloaded from the Gene Expression Omnibus (GEO) (GSE11691 and GSE120103 for training, and GSE7305 for validation). By overlapping the differentially expressed genes (DEGs), Weighted gene co-expression network analysis (WGCNA) module genes, and autophagyrelated genes (ARGs), and immune-related genes (IRGs) separately, hub genes were identified using the least absolute shrinkage and selection operator (LASSO)and support vector machine recursive feature elimination (SVM-RFE). The hub genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A hub gene-prediction model was constructed and assessed using five-fold cross-validation via five supervised machine-learning algorithms: random forest, the sequential minimal optimization (SMO), K-nearest neighbours (IBK), C4.5 decision tree (J48), and logistics regression. The area under the receiver operating characteristic curve (AUC) was adopted to assess the identification ability of characteristic genes.Results: 1,116 DEGs were obtained from the training cohort, and 22 endometriosis-related IRGs were identified by overlapping the 1,116 DEGs, 3,222 module genes, and 1,793 IRGs. Meanwhile, 45 endometriosis-related ARGs were obtained (1,928 ARGs). Subsequently, nine IRG hub genes (BST2, CCL13, CD86, CSF1, FAM3C, GREM1, ISG20, PSMB8, and S100A11) and nine ARG hub genes (GSK3A, HTR2B, RAB3GAP1, ARFIP2, BNIP3, CSF1, MAOA, PPP1R13L, and SH3GLB2) were obtained by LASSO and SVM-RFE. GO analysis indicated that the ARG hub genes responded to the regulation of autophagy and mitochondrial outer membrane permeabilization, and KEGG enrichment analysis involved serotonergic and dopaminergic synapses. GO analysis also indicated that the IRG hub genes responded to the regulation of leukocyte proliferation and mononuclear cell migration, and KEGG analysis showed enrichment involved in viral protein interaction with cytokines and cytokine receptors. The AUC of the random-forest algorithm of ARGs was 0.975 in the training cohort and 0.940 in the validation cohort, and the AUC of the SMO algorithm of IRGs was 0.907 in the training cohort and 0.8 in the validation cohort.Conclusions: Seventeen hub genes are closely associated with endometriosis. These genes are potential autophagy-and immune-related biomarkers for diagnosis and treatment of endometriosis.

Revealing the diagnostic value and immune infiltration of senescence-related genes in endometriosis: a combined single-cell and machine learning analysis

“…The chronic pain, reproductive challenges, and potential complications associated with it not only severely impact the physical health of patients but also their mental and emotional wellbeing, placing a heavy economic burden on society. We have identified a better diagnostic model than previously available ( Ji et al, 2022 ), and these data highlight the need for further research to uncover senescence-related mechanisms in EM. It has laid some foundation and direction for more in-depth research afterward.…”

Understanding the Molecular Landscape of Endometriosis: A Bioinformatics Approach to Uncover Signaling Pathways and Hub Genes

“…Their analyses, employing GO and KEGG, revealed that the identified similar genes were notably enriched in protein interactions, cellular barrier reinforcement, and cellular life dynamics (15). In a separate study, 22 endometriosis-related immune genes emerged from the overlap of 1 116 DEGs, featuring nine immune-related hub genes (BST2, CCL13, CD86, CSF1, FAM3C, GREM1, ISG20, PSMB8, S100A11) and nine ARG hub genes (GSK3A, HTR2B, RAB3GAP1, ARFIP2, BNIP3, CSF1, MAOA, PPP1R13L, SH3GLB2) (16). The heightened expression of these hub genes is intricately linked to diverse processes, including DNA methylation, protein thiol-disulfide exchange, chromatin silencing, myosin thick filament formation, and systemic development (17).…”

The mysterious association between adiponectin and endometriosis

“…The expression levels of autophagy-related genes such as microtubule-associated protein light chain 3 (LC3) and Beclin-1 have been shown to be reduced in the serum, PF, and eutopic endometrial tissue of patients with EMs compared with the levels in healthy controls ( Sui et al, 2018 ), and the level of expression of autophagy-related genes (LC3B-II) was significantly reduced in ectopic endometrium compared with that in the eutopic endometrial tissues of patients with EMs ( Li et al, 2018 ). Inhibition of autophagy can promote the expression of inflammatory cytokines, trigger inflammation and immune responses leading to autoimmune damage, enable endometrial cells to evade immune surveillance, and ultimately promote ectopic growth and implantation of ectopic endometrial cells in the peritoneal cavity ( Ji et al, 2022 ). Autophagy and apoptosis are not two independent processes but two crosstalk mechanisms.…”