{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T01:25:16Z","timestamp":1794446716275,"version":"4.9.1"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Endometriosis is a chronic inflammatory condition affecting 10% of reproductive\u2010age women. Current treatments remain limited and non\u2010curative. While its biology is largely informed by human biospecimens, sample heterogeneity and methodological constraints often limit interpretability. Using mitogen\u2010activated protein kinase 4 (MAP4K4), a cell motility and invasion regulator within the MAPK network, as a model molecule, we examined its expression in endometriosis to highlight challenges in biospecimen\u2010based research. Public endometrial microarray datasets were re\u2010analyzed using a standard limma pipeline to evaluate\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    expression across tissue and disease states. MAP4K4 mRNA and protein were then assessed in eutopic endometrium from women with and without endometriosis and in surgically excised ectopic lesions using quantitative polymerase chain reaction (qPCR), immunohistochemistry (IHC), RNA in\u00a0situ hybridization (ISH), and laser capture microdissection (LCM) coupled with qPCR.\n                    <jats:italic>In silico<\/jats:italic>\n                    analyses revealed small effect sizes and inconsistent directional change in\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    dysregulation across public datasets.\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    mRNA levels differed significantly between pipelle and full\u2010thickness eutopic biopsies. Bulk\u2010qPCR showed no significant differences in the eutopic endometrium between groups, whereas IHC demonstrated increased MAP4K4 protein in mid\u2010secretory eutopic endometrium from women with endometriosis. Whole\u2010lesion qPCR suggested higher\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    expression in ectopic versus matched eutopic tissue; however, LCM\u2010qPCR and ISH did not identify consistent compartment\u2010specific differences. Histology frequently revealed non\u2010endometrial tissue in excised ectopic lesions. These findings highlight the methodological challenges in endometriosis biospecimen research and support the need for rigorous histological validation, spatially resolved approaches, and multi\u2010modal analysis to improve the reliability and reproducibility of tissue\u2010based studies in endometriosis.\n                  <\/jats:p>","DOI":"10.1096\/fba.2026-00156","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:28:23Z","timestamp":1790004503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Methodological Pitfalls in Endometriosis Biospecimen Research: Lessons From\n                    <scp>MAP4K4<\/scp>\n                    Expression Studies"],"prefix":"10.1096","volume":"8","author":[{"given":"Dania","family":"Badran","sequence":"first","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Liverpool Women's Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Surgery The Christie Hospital NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Salvini","sequence":"additional","affiliation":[{"name":"Old College University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Drury","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Tempest","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Liverpool Women's Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Maclean","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Liverpool Women's Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0270-0150","authenticated-orcid":false,"given":"Dharani K.","family":"Hapangama","sequence":"additional","affiliation":[{"name":"Department of Women's and Children's Health, Institute of Life Course and Medical Sciences University of Liverpool  Liverpool UK"},{"name":"Liverpool Women's Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/179515"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/des073"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaf164"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hropen\/hoac026"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11111734"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/9275360"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1205509"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22044"},{"issue":"5","key":"e_1_2_11_10_1","first-page":"548","article-title":"The Action of p38 MAP Kinase and Its Inhibitors on Endometriosis","volume":"45","author":"Zhou W. 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