{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T11:57:31Z","timestamp":1769169451420,"version":"3.49.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Endometriosis is a common gynecological disorder that usually causes infertility, pelvic pain, and ovarian masses. This study aimed to mine the characteristic genes of endometriosis, and explore the regulatory mechanism and potential therapeutic drugs based on whole transcriptome sequencing data and resources from public databases, providing a theoretical basis for the diagnosis and treatment of endometriosis.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The transcriptome data of the five eutopic (EU) and ectopic (EC) endometrium samples were obtained from Beijing Obstetrics and Gynecology Hospital, Beijing, China, and dinified as the own data set. The expression and clinical data of EC and EU samples in GSE25628 and GSE7305 datasets were obtained from the GEO database (<jats:ext-link>https:\/\/www.ncbi.nlm.nih.gov\/gds<\/jats:ext-link>). Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were used to identify the endometriosis-related differentially expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted by the \u201cclusterProfiler\u201d R package. Then, characteristic genes for endometriosis were identified by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) algorithm. The expression of characteristic genes was verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western-blot. The receiver operating characteristic (ROC) curve was used to evaluate the discriminatory ability of characteristic genes. We assessed the abundance of infiltrating immune cells in each sample using MCP-counter and ImmuCellAI algorithms. The competitive endogenous RNA (ceRNA) regulatory network of characteristic genes was created by Cytoscape and potential targeting drugs were obtained in the CTD database.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 44 endometriosis-related differentially expressed genes were obtained from GSE25628 and the own dataset. Subsequently, LASSO and SVM-RFE algorithms identified four characteristic genes, namely ACLY, PTGFR, ADH1B, and MYOM1. The results of RT-PCR and western-blot were consistent with those of sequencing. The result of ROC curves indicated that the characteristic genes had powerful abilities in distinguishing EC samples from EU samples. Infiltrating immune cells analysis suggested that there was a certain difference in immune microenvironment between EC and EU samples. The characteristic genes were significantly correlated with specific differential immune cells between EC and EU samples. Then, a ceRNA regulatory network of characteristic genes was constructed and showed a total of 7, 11, 11, and 1 miRNA associated with ACLY, ADH1B, PTGFR, and MYOM1, respectively. Finally, we constructed a gene-compound network and mined 30 drugs targeting ACLY, 33 drugs targeting ADH1B, 13 drugs targeting MYOM1, and 12 drugs targeting PTGFR.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Comprehensive bioinformatic analysis was used to identify characteristic genes, and explore ceRNA regulatory network and potential therapeutic agents for endometriosis. Altogether, these findings provide new insights into the diagnosis and treatment of endometriosis.<\/jats:p>","DOI":"10.3389\/fgene.2022.902329","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T10:26:23Z","timestamp":1658485583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Analysis of characteristic genes and ceRNA regulation mechanism of endometriosis based on full transcriptional sequencing"],"prefix":"10.3389","volume":"13","author":[{"given":"Chengmao","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziran","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"242149","DOI":"10.1155\/2013\/242149","article-title":"Endometriosis: a disease that remains enigmatic","volume":"2013","author":"Aci\u00e9n","year":"2013","journal-title":"ISRN Obstet. Gynecol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1177\/2284026520940518","article-title":"Mitochondrial DNA haplogroup H association with endometriosis and possible role in inflammation and pain","volume":"12","author":"Asally","year":"2020","journal-title":"J. Endometr. Pelvic Pain Disord."},{"key":"B3","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1515\/jpm-2017-0120","article-title":"Risk factors for uterine rupture with a special interest in uterine fundal pressure: methodological issues","volume":"45","author":"Ayubi","year":"2017","journal-title":"J. Perinat. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s13059-016-1070-5","article-title":"Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression","volume":"17","author":"Becht","year":"2016","journal-title":"Genome Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1152\/physrev.00041.2015","article-title":"Non-coding RNAs in development and disease: Background, mechanisms, and therapeutic approaches","volume":"96","author":"Beermann","year":"2016","journal-title":"Physiol. Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.yexcr.2015.12.009","article-title":"Exosome derived from murine adipose-derived stromal cells: Neuroprotective effect on in vitro model of amyotrophic lateral sclerosis","volume":"340","author":"Bonafede","year":"2016","journal-title":"Exp. Cell Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/1477-7827-12-4","article-title":"Endometriosis and physical exercises: A systematic review","volume":"12","author":"Bonocher","year":"2014","journal-title":"Reprod. Biol. Endocrinol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"281","DOI":"10.2147\/IJWH.S119724","article-title":"Self-management and psychological-sexological interventions in patients with endometriosis: strategies, outcomes, and integration into clinical care","volume":"9","author":"Buggio","year":"2017","journal-title":"Int. J. Womens Health"},{"key":"B9","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.fertnstert.2012.06.029","article-title":"Pathogenesis and pathophysiology of endometriosis","volume":"98","author":"Burney","year":"2012","journal-title":"Fertil. Steril."},{"key":"B10","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.lfs.2017.10.031","article-title":"ABCA1 affects placental function via trophoblast and macrophage","volume":"191","author":"Chengmao","year":"2017","journal-title":"Life Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"4354","DOI":"10.1093\/nar\/gky286","article-title":"The number of titrated microRNA species dictates ceRNA regulation","volume":"46","author":"Chiu","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1080\/13625180701387266","article-title":"Pathogenesis of endometriosis: the role of defective 'immunosurveillance","volume":"12","author":"Christodoulakos","year":"2007","journal-title":"Eur. J. Contracept. Reprod. Health Care"},{"key":"B13","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1002\/path.2588","article-title":"Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis","volume":"219","author":"Chuang","year":"2009","journal-title":"J. Pathol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1093\/humrep\/16.9.1802","article-title":"Apoptosis in endometrial glandular and stromal cells in women with and without endometriosis","volume":"16","author":"Dmowski","year":"2001","journal-title":"Hum. Reprod."},{"key":"B15","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/humrep\/det457","article-title":"ESHRE guideline: management of women with endometriosis","volume":"29","author":"Dunselman","year":"2014","journal-title":"Hum. Reprod. Oxf. Engl."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J. Stat. Softw."},{"key":"B17","doi-asserted-by":"publisher","first-page":"996","DOI":"10.15252\/emmm.201505245","article-title":"H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis","volume":"7","author":"Ghazal","year":"2015","journal-title":"EMBO Mol. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet (London, Engl.)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1097\/GRF.0b013e3181dbda06","article-title":"Management of endometriosis-associated pain","volume":"53","author":"Hansen","year":"2010","journal-title":"Clin. Obstet. Gynecol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"795624","DOI":"10.1155\/2014\/795624","article-title":"SVM-RFE based feature selection and Taguchi parameters optimization for multiclass SVM classifier","volume":"2014","author":"Huang","year":"2014","journal-title":"Sci. World J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1093\/humrep\/dew293","article-title":"World Endometriosis Society consensus on the classification of endometriosis","volume":"32","author":"Johnson","year":"2017","journal-title":"Hum. Reprod."},{"key":"B22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1159\/000052865","article-title":"Expression of aromatase cytochrome P450 in eutopic endometrium and its application as a diagnostic test for endometriosis","volume":"48","author":"Kitawaki","year":"1999","journal-title":"Gynecol. Obstet. Invest."},{"key":"B23","doi-asserted-by":"publisher","first-page":"9","DOI":"10.3892\/mmr.2013.1755","article-title":"Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (review)","volume":"9","author":"Kobayashi","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"B24","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinforma."},{"key":"B25","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature07205","article-title":"Cancer-related inflammation","volume":"454","author":"Mantovani","year":"2008","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.mce.2016.08.017","article-title":"Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents","volume":"437","author":"McAllister","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.tem.2014.10.003","article-title":"Inflammation and nerve fiber interaction in endometriotic pain","volume":"26","author":"McKinnon","year":"2015","journal-title":"Trends Endocrinol. Metab."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1902880","DOI":"10.1002\/advs.201902880","article-title":"ImmuCellAI: a unique method for comprehensive T-cell subsets abundance prediction and its application in cancer immunotherapy","volume":"7","author":"Miao","year":"2020","journal-title":"Adv. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/humupd\/dmy014","article-title":"Non-coding RNAs in endometriosis: A narrative review","volume":"24","author":"Panir","year":"2018","journal-title":"Hum. Reprod. Update"},{"key":"B30","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s13669-017-0187-1","article-title":"Endometriosis: Epidemiology, diagnosis and clinical management","volume":"6","author":"Parasar","year":"2017","journal-title":"Curr. Obstet. Gynecol. Rep."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.1001\/jama.2018.17953","article-title":"Endometriosis","volume":"320","author":"Peiris","year":"2018","journal-title":"JAMA"},{"key":"B32","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1214\/16-AOAS920","article-title":"Robust hyperparameter estimation protects against hypervariable genes and improves power to detect differential expression","volume":"10","author":"Phipson","year":"2016","journal-title":"Ann. Appl. Stat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1016\/j.fertnstert.2014.02.012","article-title":"Treatment of pelvic pain associated with endometriosis: A committee opinion","volume":"101","year":"2014","journal-title":"Fertil. Steril."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinforma."},{"key":"B36","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1177\/1933719116654991","article-title":"Research priorities for endometriosis","volume":"24","author":"Rogers","year":"2017","journal-title":"Reprod. Sci. (Thousand Oaks, Calif.)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.14817.1","article-title":"Endometriosis: Advances and controversies in classification, pathogenesis, diagnosis, and treatment","volume":"8","author":"Rolla","year":"2019","journal-title":"F1000Research"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.1016\/j.bbadis.2017.06.018","article-title":"Challenges in endometriosis miRNA studies - from tissue heterogeneity to disease specific miRNAs","volume":"1863","author":"Saare","year":"2017","journal-title":"Biochim. Biophys. Acta. Mol. Basis Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","article-title":"A ceRNA hypothesis: the rosetta stone of a hidden RNA language","volume":"146","author":"Salmena","year":"2011","journal-title":"Cell"},{"key":"B40","doi-asserted-by":"publisher","first-page":"19384","DOI":"10.1002\/jcp.28666","article-title":"The role of inflammation, oxidative stress, angiogenesis, and apoptosis in the pathophysiology of endometriosis: Basic science and new insights based on gene expression","volume":"234","author":"Samimi","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/BF01995231","article-title":"Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation","volume":"3","author":"Sampson","year":"1927","journal-title":"Am. J. Pathol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/s0002-9378(15)30003-x","article-title":"Peritoneal endometriosis due to premenstrual disseminaton of endometrial tssue into the peritoneal cavity","volume":"15","author":"Sampson","year":"1928","journal-title":"Am. J. Obstet. Gynecol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1055\/s-2003-41320","article-title":"Endometriosis: Interaction of immune and endocrine systems","volume":"21","author":"Seli","year":"2003","journal-title":"Semin. Reprod. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4103\/0974-2727.66699","article-title":"Endometriosis \u2013 morphology, clinical presentations and molecular pathology","volume":"2","author":"Subramanian","year":"2010","journal-title":"J. Lab. Physicians"},{"key":"B46","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1093\/molehr\/gay049","article-title":"Macrophages alternatively activated by endometriosis-exosomes contribute to the development of lesions in mice","volume":"25","author":"Sun","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"B47","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/j.molmed.2018.07.004","article-title":"The immunopathophysiology of endometriosis","volume":"24","author":"Symons","year":"2018","journal-title":"Trends Mol. Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1177\/1933719115584446","article-title":"Statins as targeted \"magical pills\" for the conservative treatment of endometriosis: May potential adverse effects on female fertility Represent the \"dark side of the same coin\"? a systematic Review of literature","volume":"23","author":"Vitagliano","year":"2016","journal-title":"Reprod. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1016\/j.molcel.2011.08.018","article-title":"Molecular mechanisms of long noncoding RNAs","volume":"43","author":"Wang","year":"2011","journal-title":"Mol. Cell"},{"key":"B50","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12974-020-01752-1","article-title":"Autonomic nervous system and inflammation interaction in endometriosis-associated pain","volume":"17","author":"Wei","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"B51","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1002\/ejp.1133","article-title":"Bradykinin system is involved in endometriosis-related pain through endothelin-1 production","volume":"22","author":"Yoshino","year":"2018","journal-title":"Eur. J. Pain"},{"key":"B52","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics a J. Integr. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.902329\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T10:26:26Z","timestamp":1658485586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.902329\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":53,"alternative-id":["10.3389\/fgene.2022.902329"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.902329","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"902329"}}