{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T09:10:29Z","timestamp":1784279429604,"version":"3.55.0"},"reference-count":22,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epigenetic dysregulation is increasingly recognized as an important contributor to ovarian carcinogenesis, and may provide novel diagnostic and prognostic biomarkers. This study evaluated DNA methylation and mRNA expression of SEPT9 and AKR1B1 in ovarian cancer and benign ovarian lesions and assessed their clinical significance. Tissue samples were obtained from 27 patients with ovarian cancer and 29 patients with benign ovarian lesions. DNA methylation was analyzed by pyrosequencing and mRNA expression by real-time PCR. Associations with clinicopathological variables, serum CA125 and HE4 concentrations, diagnostic performance, and survival outcomes were evaluated. Receiver operating characteristic (ROC) analysis, multivariable logistic regression, Kaplan\u2013Meier analysis, and Cox regression models were performed. Multiple testing was controlled using the Benjamini\u2013Hochberg false discovery rate procedure. Ovarian cancer tissues demonstrated significantly lower SEPT9 methylation (q = 0.008), higher AKR1B1 methylation (q = 0.0008), and lower AKR1B1 mRNA expression (q = 0.035) compared with benign ovarian lesions. SEPT9 methylation showed the highest diagnostic accuracy (AUC = 0.741). Both SEPT9 methylation (OR = 0.92, p = 0.014) and AKR1B1 methylation (OR = 9.69, p = 0.008) remained independently associated with ovarian cancer after adjustment for age and menopausal status. Low AKR1B1 mRNA expression was associated with shorter progression-free survival (p = 0.0007). These findings indicate that SEPT9 methylation and AKR1B1 dysregulation are associated with ovarian cancer. SEPT9 methylation demonstrated the best discriminative ability among the evaluated biomarkers. Further validation in larger independent cohorts is warranted.<\/jats:p>","DOI":"10.3390\/ijms27146336","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T03:12:38Z","timestamp":1784257958000},"page":"6336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA Methylation and mRNA Expression of SEPT9 and AKR1B1 in Ovarian Cancer: Diagnostic and Prognostic Implications"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-2153","authenticated-orcid":false,"given":"Mateusz","family":"Koz\u0142owski","sequence":"first","affiliation":[{"name":"Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-5052","authenticated-orcid":false,"given":"Dominika","family":"Borzyszkowska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4600-8920","authenticated-orcid":false,"given":"Micha\u0142","family":"Lubkowski","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3162-4870","authenticated-orcid":false,"given":"Nina","family":"Komaniecka","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Al. Powsta\u0144c\u00f3w Wlkp. 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Mikulka","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology and Reconstructive Gynecology, Department of Obstetrics and Gynecology with the High-Risk Pregnancy Unit, Independent Public Specialist Healthcare Centre \u201cZdroje\u201d, 70-780 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6256-5695","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Birger","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacodynamics, Pomeranian Medical University in Szczecin, Plac Polskiego Czerwonego Krzy\u017ca 1, 71-244 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0855-6471","authenticated-orcid":false,"given":"Piotr","family":"Kolczewski","sequence":"additional","affiliation":[{"name":"Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6425-1648","authenticated-orcid":false,"given":"Agnieszka","family":"Brodowska","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Endocrinology and Gynecological Oncology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7788","authenticated-orcid":false,"given":"Mateusz","family":"Kurzawski","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacodynamics, Pomeranian Medical University in Szczecin, Plac Polskiego Czerwonego Krzy\u017ca 1, 71-244 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-8640","authenticated-orcid":false,"given":"Agnieszka","family":"Kempinska-Podhorodecka","sequence":"additional","affiliation":[{"name":"Department of Functional Anatomy, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Cymbaluk-P\u0142oska","sequence":"additional","affiliation":[{"name":"Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University in Szczecin, Al. Powsta\u0144c\u00f3w Wielkopolskich 72, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.soncn.2019.02.001","article-title":"Ovarian Cancer: An Integrated Review","volume":"35","author":"Stewart","year":"2019","journal-title":"Semin. Oncol. 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