Diagnostic gene biomarkers for predicting immune infiltration in endometriosis

Abstract

Objective To determine the potential diagnostic markers and extent of immune cell infiltration in endometriosis (EMS). Methods Two published profiles (GSE7305 and GSE25628 datasets) were downloaded, and the candidate biomarkers were identified by support vector machine recursive feature elimination analysis and a Lasso regression model. The diagnostic value and expression levels of biomarkers in EMS were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blotting, then further validated in the GSE5108 dataset. CIBERSORT was used to estimate the composition pattern of immune cell components in EMS. Results One hundred and fifty-three differential expression genes (DEGs) were identified between EMS and endometrial with 83 upregulated and 51 downregulated genes. Gene sets related to arachidonic acid metabolism, cytokine–cytokine receptor interactions, complement and coagulation cascades, chemokine signaling pathways, and systemic lupus erythematosus were differentially activated in EMS compared with endometrial samples. Aquaporin 1 (AQP1) and ZW10 binding protein (ZWINT) were identified as diagnostic markers of EMS, which were verified using qRT-PCR and western blotting and validated in the GSE5108 dataset. Immune cell infiltrate analysis showed that AQP1 and ZWINT were correlated with M2 macrophages, NK cells, activated dendritic cells, T follicular helper cells, regulatory T cells, memory B cells, activated mast cells, and plasma cells. Conclusion AQP1 and ZWINT could be regarded as diagnostic markers of EMS and may provide a new direction for the study of EMS pathogenesis in the future.

Identification of iron metabolism-related predictive markers of endometriosis and endometriosis-relevant ovarian cancer

“…Endometriosis has long been considered an autoimmune disease given that the increased number and activation of peritoneal macrophages and the decreased cytotoxicity of T cells and natural killer cells are common alterations in cellular immunity and lead to inadequate clearance of ectopic endometrial cells from the peritoneal cavity. [ 59 ] Although these results conflict with previous research results, [ 60 , 61 ] it is considered that sample error may have occurred. The inflammatory response activated by these immune cells is also associated with the oxidative stress caused by iron overload as described above, further confirming the relevance of iron metabolism in endometriosis.…”

Construction and evaluation of endometriosis diagnostic prediction model and immune infiltration based on efferocytosis-related genes

“…These studies have also identified diverse Frontiers in Molecular Biosciences frontiersin.org biomarker genes implicated in EM, such as CCR5, MRC1, SYK, NOTCH3, SNAPC2, and PTOV1 (Akter et al, 2019;Wang et al, 2022). Xie et al, 2022 suggested that the overexpression levels of DZWINT and AQP1 on endometriotic tissue mediated underlying immune system-associated pathology between M2 macrophages, activated mast cells, memory B cells, and activated NK cells, etc. Frontiers in Molecular Biosciences frontiersin.org…”

Identification and validation of risk score model based on gene set activity as a diagnostic biomarker for endometriosis

“…EMS patients may suffer from dysmenorrhea, irregular uterine bleeding, chronic pelvic pain, infertility, and other complications [ 3 ]. These symptoms considerably decrease patients' quality of life, while the increased utilization of assisted reproductive technology due to infertility raises social costs as well [ 4 ]. Therefore, it is imperative to investigate the pathogenesis and treatment of EMS.…”