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This represents a huge burden for women\u2019s health since all women presenting with bleeding will undergo sequential invasive tests, which are avoidable for 90\u201395% of those women who do not have EC. Methods: This study aimed to evaluate the potential of cervical samples collected with five different devices as a source of protein biomarkers to diagnose EC. We evaluated the protein quantity and the proteome composition of five cervical sampling methods. Results: Samples collected with a Rovers Cervex Brush\u00ae and the HC2 DNA collection device, Digene, were the most suitable samples for EC proteomic studies. Most proteins found in uterine fluids were also detected in both cervical samples. We then conducted a clinical retrospective study to assess the expression of 52 EC-related proteins in 41 patients (22 EC; 19 non-EC), using targeted proteomics. We identified SERPINH1, VIM, TAGLN, PPIA, CSE1L, and CTNNB1 as potential protein biomarkers to discriminate between EC and symptomatic non-EC women with abnormal uterine bleeding in cervical fluids (AUC &gt; 0.8). Conclusions: This study opens an avenue for developing non-invasive protein-based EC diagnostic tests, which will improve the standard of care for gynecological patients.<\/jats:p>","DOI":"10.3390\/cancers15030911","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T05:33:53Z","timestamp":1675229633000},"page":"911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cervical Fluids Are a Source of Protein Biomarkers for Early, Non-Invasive Endometrial Cancer Diagnosis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2547-7916","authenticated-orcid":false,"given":"Elena","family":"Martinez-Garcia","sequence":"first","affiliation":[{"name":"Proteomics of Cellular Signaling, Department of Infection and Immunity, Luxembourg Institute of Health, 1445 Strassen, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Coll-de la Rubia","sequence":"additional","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Aut\u00f2noma de Barcelona, CIBERONC, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Lesur","sequence":"additional","affiliation":[{"name":"Quantitative Biology Unit, Luxembourg Institute of Health, 1445 Strassen, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3647-8623","authenticated-orcid":false,"given":"Gunnar","family":"Dittmar","sequence":"additional","affiliation":[{"name":"Proteomics of Cellular Signaling, Department of Infection and Immunity, Luxembourg Institute of Health, 1445 Strassen, Luxembourg"},{"name":"Department of Life Sciences and Medicine, University of Luxembourg, 4367 Esch-sur-Alzette, Luxembourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-5590","authenticated-orcid":false,"given":"Antonio","family":"Gil-Moreno","sequence":"additional","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Aut\u00f2noma de Barcelona, CIBERONC, 08035 Barcelona, Spain"},{"name":"Gynaecological Department, Vall Hebron University Hospital, CIBERONC, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cabrera","sequence":"additional","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Aut\u00f2noma de Barcelona, CIBERONC, 08035 Barcelona, Spain"},{"name":"Gynaecological Department, Vall Hebron University Hospital, CIBERONC, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0302-4828","authenticated-orcid":false,"given":"Eva","family":"Colas","sequence":"additional","affiliation":[{"name":"Biomedical Research Group in Gynecology, Vall Hebron Institute of Research, Universitat Aut\u00f2noma de Barcelona, CIBERONC, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. 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