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Study on the potential diagnostic biomarker of endometriosis
LIU Yu, ZHANG Wen-zhu, LIN Geng
Chinese Journal of Practical Gynecology and Obstetrics ›› 2026, Vol. 42 ›› Issue (2) : 230-237.
PDF(5633 KB)
PDF(5633 KB)
Study on the potential diagnostic biomarker of endometriosis
Objective To explore the gene network underlying EMs，identify potential diagnostic biomarkers，validate their diagnostic efficacy using clinical serum specimens，and elucidate the association between core genes and immune microenvironment. Methods Transcriptomic datasets GSE7305 （10 healthy controls， 10 EMs cases） and GSE51981 （34 healthy controls， 49 EMs cases） from the Gene Expression Omnibus （GEO） database were integrated. Batch effects were corrected by the ComBat algorithm， and differentially expressed genes were screened. Weighted Gene Co-expression Network Analysis （WGCNA） was used to identify EMs-related molecular modules，and 113 machine learning algorithms were employed to construct a diagnostic model， whose efficacy was validated by bootstrap， calibration curves and clinical decision curves. CIBERSORT was applied to analyze immune cell infiltration; combined with single-sample Gene Set Enrichment Analysis （ssGSEA） and Shapley Additive exPlanations （SHAP） analysis， the functions of core genes and their diagnostic contributions were clarified. Additionally， 30 EMs patients and 20 non-EMs controls who visited Shengjing Hospital of China Medical University from March to May 2025 were selected， and the expression of core genes and their encoded proteins in serum was verified by enzyme-linked immunosorbent assay （ELISA）， polymerase chain reaction （PCR） and Western blot. Results Compared with healthy people，a total of 711 DEGs were identified in EMs patients （308 upregulated；403 downregulated）. WGCNA indicated that the greenyellow module had the strongest positive correlation with EMs phenotype. The top 10 genes of the 58 DEGs in this module，ranked by absolute fold change，were evaluated through 113 machine learning models，with random forest （RF） demonstrating optimal diagnostic efficacy for EMs （C-index=0.991）. Subsequently，core genes C10orf54，CALCOCO1，ADAT1，and KIF21A were screened out. SHAP analysis indicated C10orf54 as the primary contributor to disease prediction，and the nomogram model showed that C10orf54 had the highest weight in the disease progression of EMs. Clinical specimens validated that the expression of C10orf54 mRNA was downregulated in the serum of EMs patients （P<0.05）， and C10orf54-encoded protein VISTA was significantly upregulated in the serum of EMs patients（P<0.0001）. ssGSEA revealed that C10orf54 was involved in the regulation of copper ion stress and cell cycle. Immune cell infiltration analysis indicated that the proportions of activated immune cells such as memory B cells and CD8+ T cells in EMs patients were increased； what's more，C10orf54 expression was positively correlated with activated immune cells. Conclusions C10orf54 may serve as a potential diagnostic biomarker for EMs. Its aberrant expression is closely associated with dysregulation of the immune microenvironment，providing a novel molecular target for early diagnosis and immune-targeted therapy of EMs.
endometriosis / diagnostic biomarkers / immune microenvironment / clinical research
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Endometriosis is a common disease affecting 5-10% of women of reproductive age globally. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and delivery of effective therapy is prolonged. Identification and prompt treatment of endometriosis are essential and facilitated by accurate clinical diagnosis. Endometriosis is classically defined as a chronic, gynaecological disease characterised by endometrial-like tissue present outside of the uterus and is thought to arise by retrograde menstruation. However, this description is outdated and no longer reflects the true scope and manifestations of the disease. The clinical presentation is varied, the presence of pelvic lesions is heterogeneous, and the manifestations of the disease outside of the female reproductive tract remain poorly understood. Endometriosis is now considered a systemic disease rather than a disease predominantly affecting the pelvis. Endometriosis affects metabolism in liver and adipose tissue, leads to systemic inflammation, and alters gene expression in the brain that causes pain sensitisation and mood disorders. The full effect of the disease is not fully recognised and goes far beyond the pelvis. Recognition of the full scope of the disease will facilitate clinical diagnosis and allow for more comprehensive treatment than currently available. Progestins and low-dose oral contraceptives are unsuccessful in a third of symptomatic women globally, probably as a result of progesterone resistance. Oral gonadotropin-releasing hormone (GnRH) antagonists constitute an effective and tolerable therapeutic alternative when first-line medications do not work. The development of GnRH antagonists has resulted in oral drugs that have fewer side-effects than other therapies and has allowed for rapid movement between treatments to optimise and personalise endometriosis care. In this Review, we discuss the latest understanding of endometriosis as a systemic disease with multiple manifestations outside the parameters of classic gynaecological disease.Copyright © 2021 Elsevier Ltd. All rights reserved.
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Endometriosis is a prevalent gynecological condition associated with pelvic pain and infertility. Despite more than a century of research, the etiology of endometriosis still eludes scientific consensus. This lack of clarity has resulted in suboptimal prevention, diagnosis, and treatment options. Evidence of genetic contributors to endometriosis is interesting but limited; however, significant progress has been made in recent years in identifying epigenetic role in the pathogenesis of endometriosis through clinical studies, in vitro cell culture experiments, and in vivo animal models. The predominant findings include endometriosis-related differential expression of DNA methyltransferases and demethylases, histone deacetylases, methyltransferases, and demethylases, and regulators of chromatin architecture. There is also an emerging role for miRNAs in the control of epigenetic regulators in the endometrium and endometriosis. Changes in these epigenetic regulators result in differential chromatin organization and DNA methylation with consequences for gene expression independent of a genetic sequence. Epigenetically altered expression of genes related to steroid hormone production and signaling, immune regulation, and endometrial cell identity and function have all been identified and appear to play into the pathophysiological mechanisms of endometriosis as well as resulting infertility. This review summarizes and critically discusses early seminal findings, the ever-growing recent evidence of epigenetic contributions to the pathophysiology of endometriosis, and implications for proposed epigenetically targeted therapeutics.© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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Endometriosis is a common gynecological disorder seen in women and is characterized by chronic pelvic pain and infertility. This disorder is becoming more prevalent with increased morbidity. The etiology of endometriosis remains to be fully elucidated, which will lead to improved therapeutic options. In this review, we will evaluate the biochemical mechanisms leading to oxidative stress and their implication in the pathophysiology of endometriosis, as well as potential treatments that target these processes. A comprehensive exploration of previous research revealed that endometriosis is associated with elevated reactive oxygen species and oxidation products, decreased antioxidants and detoxification enzymes, and dysregulated iron metabolism. High levels of oxidative stress contributed to inflammation, extracellular matrix degradation, angiogenesis, and cell proliferation, which may explain its role in endometriosis. Endometriosis-associated pain was attributed to neurogenic inflammation and a feed-forward mechanism involving macrophages, pro-inflammatory cytokines, and pain-inducing prostaglandins. N-acetylcysteine, curcumin, melatonin, and combined vitamin C and E supplementation displayed promising results for the treatment of endometriosis, but further research is needed for their use in this population.
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To evaluate HOXA10 expression in endometriosis.Laboratory study using human tissue.Academic research center.Eutopic endometrial tissue was collected from 20 fertile women without endometriosis. Ectopic endometrial tissues from pelvic peritoneum, ovary, and lung parenchyma were collected from 20 women undergoing surgery for endometriosis.HOXA10 protein expression and localization with immunohistochemistry.Quantitative analysis of HOXA10 expression, according to H score.Both eutopic and ectopic endometrial tissue expressed HOXA10. Ectopic endometrial tissue had lower stromal HOXA10 expression compared with eutopic endometrium. The mean H score for stromal expression of HOXA10 was 7.6 in eutopic endometrium and 1.3 in ectopic endometrial tissue. Glandular epithelium from both eutopic and ectopic endometrium had similarly low HOXA10 expression. HOXA10 was also expressed at low levels in lung parenchyma containing endometriosis and in ovarian endometriomas.HOXA10 is expressed in endometriosis at locations outside of the normal HOXA10 expression domain, where it is likely necessary to impart endometrial developmental identity on endometriosis. HOXA10 might be necessary for "de novo" endometrial development. However, the diminished expression of HOXA10 in ectopic endometrium might not allow for normal endometrial development and might contribute to the pathogenesis of endometriosis by creating P resistance.
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Cuproptosis is a new form of programmed cell death, which is associated with the mitochondrial TCA (tricarboxylic acid) cycle. But the functions of cuproptosis in endometriosis progression are still unknown. Here, we find that cuproptosis suppresses the growth of endometriosis cells and the growth of ectopic endometrial tissues in a mouse model. FDX1 as a key regulator in cuproptosis pathway could promote cuproptosis in endometriosis cells. Interestingly, FDX1 interacts with G6PD, and reduces its protein stability, which predominantly affects the cellular redox-regulating systems. Then, the reduced G6PD activity enhances cuproptosis via down-regulating NADPH and GSH levels. Collectively, our study demonstrates that FDX1 mediates cuproptosis in endometriosis via G6PD pathway, resulting in repression of endometriosis cell proliferation and metastasis.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.
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Plasmacytoid dendritic cells (pDC) have been regarded as the "professional type I IFN-producing cells" of the immune system following viral recognition that relies on the expression of TLR7 and TLR9. Furthermore, pDC link the innate and adaptive immune systems via cytokine production and Ag presentation. More recently, their ability to induce tolerance and cytotoxicity has been added to their "immune skills." Such a broad range of actions, resembling the diverse functional features of a Swiss army knife, requires strong and prompt molecular regulation to prevent detrimental effects, including autoimmune pathogenesis or tumor escape. Over the last decades, we and other investigators have started to unravel some aspects of the signaling pathways that regulate the various functions of human pDC. In this article, we review aspects of the molecular regulatory mechanisms to control pDC function in light of their multifaceted roles during immunity, autoimmunity, and cancer. Copyright © 2014 by The American Association of Immunologists, Inc.
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In the post genomic era where virtually all the genes and the proteins are known, an important task is to provide a comprehensive analysis of the expression of important classes of genes, such as those that are required for intracellular transport. We report the comprehensive analysis of the Kinesin Superfamily, which is the first and only large protein family whose constituents have been completely identified and confirmed in silico and at the cDNA, mRNA level. In FANTOM2, we have found 90 clones from 33 Kinesin Superfamily Protein (KIF) gene loci. The clones were analyzed in reference to sequence state, library of origin, detection methods, and alternative splicing. More than half of the representative transcriptional units (TU) were full length. The FANTOM2 library also contains novel splice variants previously unreported. We have compared and evaluated various protein classification tools and protein search methods using this data set. This report provides a foundation for future research of the intracellular transport along microtubules and proves the significance of intracellular transport protein transcripts as part of the transcriptome.
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