{"paper_id":"03cea932-c154-446d-98d9-b2ffb31a1023","body_text":"INTRODUCTION \nReview question / Objective 1. We \nanalyzed RNA array data to identify \nexpression differences between eutopic \nendometrium without and with endometriosis \n2. We analyzed RNA array data to identify \nexpression di fferences between eutopic \nendometrium and ecoptic endometriosis\n3. Then we have been interested whether \nepithelial-mesenchymal transition (EMT) is involved \nin the pathogenesis of endometriosis\n4. We compared the initial steps of the seed and \nsoil hypothesis of cancer with the pathogenesis of \nendometriosis. \nRationale We wanted to see whether expression \nchanges in the endometrium might contribute to \nendometriosis and whether EMT is involved in the \npathogenesis. Furthermore, we wanted to find out \nwhether the seed and soil hypothesis of \ntumorigenesis is comparable to endometriosis. \nCondition being studied We s t u d i e d \nendometriosis which is de fined by ectopic \nendometrium mainly in the pelvis. The disease is \ncharacterized mainly by extreme pelvic pain and/or \ninfertility. \nMETHODS \nSearch strategy Medline with PubMed. \nParticipant or population Patients with and \nwithout endometriosis are included, however, only \nindirectly, because we studied the RNA \nexpressdion profile of these patients. \nIntervention Not applicable. \nComparator Not applicable. \nStudy designs to be included Only scientific \nstudies showing comparisons between eutopic \nendometrium without and with endometriosis and \nbetween eutopic and ectopic endometriosis will be \nincluded. \nINPLASY 1\nInternational Platform of Registered Systematic Review and Meta-analysis Protocols\nINPLASYThe different gene expression profile in eutopic and \nectopic endometrium sheds new light on the \nendometrial seed in endometriosis\nRiaz, MA; Mecha, EO; Omwandho, COA; Zeppernick, F; \nMeinhold-Heerlein, I; Konrad, L.\nADMINISTRATIVE INFORMATION  \nSupport -  Not applicable. \nReview Stage at time of this submission - Completed but not \npublished. \nConflicts of interest - None declared. \nINPLASY registration number: INPLASY202460009 \nAmendments - This protocol was registered with the International \nPlatform of Registered Systematic Review and Meta-Analysis Protocols \n(INPLASY) on 04 June 2024 and was last updated on 04 June 2024.\nCorresponding author: \nLutz Konrad\nlutz.konrad@gyn.med.uni-giessen.de\nAuthor Affiliation:                   \nInstitute of Gynecology and \nObstetrics.\nRiaz et al. INPLASY protocol 202460009. doi:10.37766/inplasy2024.6.0009\nRiaz et al. INPLASY protocol 202460009. doi:10.37766/inplasy2024.6.0009 Downloaded from https://inplasy.com/inplasy-2024-6-0009/\nINPLASY202460009\ndoi: 10.37766/inplasy2024.6.0009 \nReceived: 04 June 2024\nPublished: 04 June 2024\n\nEligibility criteria Inclusion criteria\n• Study desing: Experimental\n• Source: Peer reviewed journals\n• Study subjects: humans\n• Language: N/A\n• Disease: Endometriosis\n• Technique for analysis: gene expression by array \nExclusion criteria\n• Missing data\n• Duplicates.\nInformation sources PubMed, contact with \nauthors.\nMain outcome(s) We found that the similarity \nbetween eutopic endometrium without and with \nendometriosis is extremely high (~99.1%). In \ncontrast, the eutopic endometrium of patients with \nendometriosis has a similarity of only 95.3% with \nthe ectopic endometrium. Analysis of EMT-\nassociated genes revealed only minor differences \nin mRNA expression levels of claudin family \nmembers without loss of other cell-cell junctions \nthat are critical for the epithelial phenotype. The \narray data suggest that the changes in the eutopic \nendometrium (=seed) are quite subtle at the \nbeginning of the disease and that most of the \ndifferences occur after implantation into ectopic \nlocations (=soil). We could show that the initial \nsteps of tumorigenesis are clearly di fferent to \nendometriosis. \nQuality assessment / Risk of bias analysis We \nchecked each publication whether the authors \nprovided all data about the array, the methods \nused, and the study population and whether all \ndata about gene expression have been provided. \nRisk of bias analysis is not applicable. \nStrategy of data synthesis The data will be \nsummarized as percentage of gene expression \nchanges between the different groups.\nChanges in the mRNA expression of EMT-\nassociated genes will be analyzed also. \nSubgroup analysis Not applicable. \nSensitivity analysis Not applicable. \nCountry(ies) involved Deutschland. \nOther relevant information We want to register \nthe study retrospectively, because we did not \nknow that scientific systematic reviews now also \nneed a registration code in order to be published. \n30 years ago when we started to write scientific \nreviews this was not necessary and the people \nfrom the platform PROSPERO still think that \nscientific systematic reviews do not need to be \nregistered. Unfortunately, we need the registration \ncode that the review will be published.\nKeywords endometrium; endometriosis; epithelial-\nmesenchymal transition (EMT); claudins; keratins; \nseed and soil. \nContributions of each author \nAuthor 1 - Muhammad A Riaz - Collection of \nmanuscripts, writing and proof-reading.\nAuthor 2 - Ezekiel Onyonka Mecha - Suggestions, \nwriting and proofreading.\nAuthor 3 - Charles OA Omwandho - Suggestions, \nwriting and proofreading.\nAuthor 4 - Felix Zeppernick - Suggestions, writing \nand proofreading.\nAuthor 5 - Ivo Meinhold-Heerlein - Suggestions, \nwriting and proofreading.\nAuthor 6 - Lutz Konrad - Whole concept, literature \nsearch, writing and proofreading.\nEmail: lutz.konrad@gyn.med.uni-giessen.de\nINPLASY 2Riaz et al. INPLASY protocol 202460009. doi:10.37766/inplasy2024.6.0009\nRiaz et al. INPLASY protocol 202460009. doi:10.37766/inplasy2024.6.0009 Downloaded from https://inplasy.com/inplasy-2024-6-0009/","source_license":"CC0","license_restricted":false}