{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:31:14Z","timestamp":1789029074193,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006370","name":"Small Business Innovation Research","doi-asserted-by":"publisher","award":["R44HD097750-01"],"award-info":[{"award-number":["R44HD097750-01"]}],"id":[{"id":"10.13039\/100006370","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>(1) Background: Endometriosis is characterized by the presence of endometrial glands and stroma outside of the uterus and is often associated with severe pelvic pain and infertility. Our study explored the utilization of B-Cell Lymphoma 6 (BCL6) and Sirtuin 1 (SIRT1) as potential biomarkers in serum, plasma, urine, and cervical mucus for a non-invasive diagnostic test for endometriosis. BCL6 was chosen based on its previously reported elevated expression in endometrial biopsies, and SIRT1 is co-expressed and upregulated in the endometrium of women with endometriosis. (2) Methods: BCL6 and SIRT1 levels were measured using enzyme-linked immunoassay (ELISA) in samples from 20 women with endometriosis (ten with stages I\/II and ten with stages III\/IV) and ten women without endometriosis. (3) Results: Levels of SIRT1 in sera showed a statistically significant elevation in advanced stages III\/IV compared to controls and stages I\/II. No significant differences were found in other bodily fluids for SIRT1 or any bodily fluids tested for BCL6. (4) Conclusions: These results suggest some potential of SIRT1 expression within serum as a predictor of advanced asymptomatic stages of endometriosis. Using immunohistochemistry (IHC) staining and H-SCORE values for the elevated BCL6 (and potentially SIRT1) levels in endometrial biopsy samples seems to have higher diagnostic potential based on the previously published studies.<\/jats:p>","DOI":"10.3390\/cimb43030096","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T21:39:29Z","timestamp":1632865169000},"page":"1350-1360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Evaluation of BCL6 and SIRT1 as Non-Invasive Diagnostic Markers of Endometriosis"],"prefix":"10.3390","volume":"43","author":[{"given":"Alison M.","family":"Sansone","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke V.","family":"Hisrich","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Brandt","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William F.","family":"Abel","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9102-6625","authenticated-orcid":false,"given":"Zachary","family":"Bowens","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Prisma Health Upstate, 701 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bailey B.","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9287-7683","authenticated-orcid":false,"given":"Avery T.","family":"Funkhouser","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Schammel","sequence":"additional","affiliation":[{"name":"Pathology Associates of Greenville, 701 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Prisma Health Upstate, 701 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Lessey","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest University Baptist Hospital, 1 Medical Center Blvd, Winston-Salem, NC 27157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7669-3120","authenticated-orcid":false,"given":"Anna V.","family":"Blenda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, 607 Grove Rd., Greenville, SC 29605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1001\/jama.1908.25310280023002d","article-title":"Adenomyoma of the uterus","volume":"L","author":"Cullen","year":"1908","journal-title":"J. Am. Med. Assoc."},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet (Lond. UK)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1074-3804(05)80830-8","article-title":"Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain","volume":"2","author":"Carter","year":"1994","journal-title":"J. Am. Assoc. Gynecol. Laparosc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1016\/S0015-0282(03)00155-9","article-title":"Diagnostic accuracy of laparoscopy, magnetic resonance imaging, and histopathologic examination for the detection of endometriosis","volume":"79","author":"Stratton","year":"2003","journal-title":"Fertil. Steril."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.fertnstert.2011.05.090","article-title":"World Endometriosis Research Foundation Global Study of Women\u2019s Health consortium Impact of endometriosis on quality of life and work productivity: A multicenter study across ten countries","volume":"96","author":"Nnoaham","year":"2011","journal-title":"Fertil. Steril."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1093\/humrep\/des073","article-title":"The burden of endometriosis: Costs and quality of life of women with endometriosis and treated in referral centres","volume":"27","author":"Simoens","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/humupd\/dmm010","article-title":"Endometriosis: Cost estimates and methodological perspective","volume":"13","author":"Simoens","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s12325-018-0667-3","article-title":"Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States","volume":"35","author":"Soliman","year":"2018","journal-title":"Adv. Ther."},{"key":"ref_10","first-page":"CD001751","article-title":"Nonsteroidal anti-inflammatory drugs for dysmenorrhoea","volume":"2015","author":"Marjoribanks","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1097\/GRF.0000000000000292","article-title":"Medical Management of Endometriosis","volume":"60","author":"Rafique","year":"2017","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","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":"ref_13","doi-asserted-by":"crossref","unstructured":"Sourial, S., Tempest, N., and Hapangama, D.K. (2014). Theories on the pathogenesis of endometriosis. Int. J. Reprod. Med., 2014.","DOI":"10.1155\/2014\/179515"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/S0002-9378(15)30003-X","article-title":"Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity","volume":"14","author":"Sampson","year":"1927","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","first-page":"151","article-title":"Retrograde menstruation in healthy women and in patients with endometriosis","volume":"64","author":"Halme","year":"1984","journal-title":"Obstet. Gynecol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chantalat, E., Valera, M.-C., Vaysse, C., Noirrit, E., Rusidze, M., Weyl, A., Vergriete, K., Buscail, E., Lluel, P., and Fontaine, C. (2020). Estrogen Receptors and Endometriosis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21082815"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1055\/s-0034-1376355","article-title":"Homeostasis imbalance in the endometrium of women with implantation defects: The role of estrogen and progesterone","volume":"32","author":"Lessey","year":"2014","journal-title":"Semin. Reprod. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1055\/s-0035-1554053","article-title":"Molecular biology of endometriosis: From aromatase to genomic abnormalities","volume":"33","author":"Bulun","year":"2015","journal-title":"Semin. Reprod. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1210\/er.2012-1043","article-title":"Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer","volume":"34","author":"Kim","year":"2013","journal-title":"Endocr. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1111\/aogs.13156","article-title":"Progesterone resistance in endometriosis: Origins, consequences and interventions","volume":"96","author":"Patel","year":"2017","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6765","DOI":"10.1038\/s41598-017-04577-w","article-title":"KRAS Activation and over-expression of SIRT1\/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance","volume":"7","author":"Yoo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1210\/me.2003-0133","article-title":"Mitogenic Activity of Estrogens in Human Breast Cancer Cells Does Not Rely on Direct Induction of Mitogen-Activated Protein Kinase\/Extracellularly Regulated Kinase or Phosphatidylinositol 3-Kinase","volume":"18","author":"Gaben","year":"2004","journal-title":"Mol. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Marquardt, R.M., Kim, T.H., Shin, J.-H., and Jeong, J.-W. (2019). Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153822"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1093\/humupd\/dmz005","article-title":"Endometriosis and nuclear receptors","volume":"25","author":"Yilmaz","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5262","DOI":"10.1073\/pnas.90.11.5262","article-title":"Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas","volume":"90","author":"Baron","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6947","DOI":"10.1073\/pnas.93.14.6947","article-title":"BCL-6, a POZ\/zinc-finger protein, is a sequence-specific transcriptional repressor","volume":"93","author":"Chang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/WOX.0b013e31817dc522","article-title":"Role of the Transcriptional Repressor BCL6 in Allergic Response and Inflammation","volume":"1","author":"Arima","year":"2008","journal-title":"World Allergy Organ. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1038\/sj.leu.2404856","article-title":"Distinctive patterns of BCL6 molecular alterations and their functional consequences in different subgroups of diffuse large B-cell lymphoma","volume":"21","author":"Iqbal","year":"2007","journal-title":"Leukemia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5257","DOI":"10.1182\/blood.V87.12.5257.bloodjournal87125257","article-title":"BCL-6 expression during B-cell activation","volume":"87","author":"Allman","year":"1996","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.1182\/blood-2002-11-3387","article-title":"Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma","volume":"101","author":"Pasqualucci","year":"2003","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0065-2776(10)05007-8","article-title":"BCL6: Master regulator of the germinal center reaction and key oncogene in B cell lymphomagenesis","volume":"105","author":"Basso","year":"2010","journal-title":"Adv. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1177\/1933719116649711","article-title":"Endometrial BCL6 Overexpression in Eutopic Endometrium of Women With Endometriosis","volume":"23","author":"Lessey","year":"2016","journal-title":"Reprod. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20070140","article-title":"Sirtuins in mammals: Insights into their biological function","volume":"404","author":"Michan","year":"2007","journal-title":"Biochem. J."},{"key":"ref_34","unstructured":"(2021, August 06). SIRT1 Sirtuin 1 [Homo Sapiens (Human)]-Gene-NCBI, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene\/23411."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1006\/bbrc.1999.0897","article-title":"Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity","volume":"260","author":"Frye","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/scientificamerican0306-48","article-title":"Unlocking the secrets of longevity genes","volume":"294","author":"Sinclair","year":"2006","journal-title":"Sci. Am."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1093\/emboj\/21.10.2383","article-title":"Human SIR2 deacetylates p53 and antagonizes PML\/p53-induced cellular senescence","volume":"21","author":"Langley","year":"2002","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0092-8674(01)00524-4","article-title":"Negative control of p53 by Sir2alpha promotes cell survival under stress","volume":"107","author":"Luo","year":"2001","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0092-8674(01)00527-X","article-title":"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase","volume":"107","author":"Vaziri","year":"2001","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1478-811X-9-11","article-title":"Mammalian Sirt1: Insights on its biological functions","volume":"9","author":"Rahman","year":"2011","journal-title":"Cell Commun. Signal."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cell.2005.11.002","article-title":"The Enigmatic Role of Sir2 in Aging","volume":"123","author":"Kennedy","year":"2005","journal-title":"Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1177\/1947601912475079","article-title":"The Roles of SIRT1 in Cancer","volume":"4","author":"Lin","year":"2013","journal-title":"Genes Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ncrna.2021.02.002","article-title":"MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis","volume":"6","author":"Rezk","year":"2021","journal-title":"Non-Coding RNA Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/S0015-0282(16)55216-9","article-title":"Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology*\u2020","volume":"58","author":"Buyalos","year":"1992","journal-title":"Fertil. Steril."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/S0015-0282(98)00204-0","article-title":"The follicular and endocrine environment in women with endometriosis: Local and systemic cytokine production","volume":"70","author":"Pellicer","year":"1998","journal-title":"Fertil. Steril."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1093\/humrep\/dev050","article-title":"Aberrant activation of signal transducer and activator of transcription-3 (STAT3) signaling in endometriosis","volume":"30","author":"Kim","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1093\/intimm\/dxl041","article-title":"JunD\/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells","volume":"18","author":"Arguni","year":"2006","journal-title":"Int. Immunol."}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/3\/96\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:06:21Z","timestamp":1760166381000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/43\/3\/96"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,28]]},"references-count":47,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cimb43030096"],"URL":"https:\/\/doi.org\/10.3390\/cimb43030096","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,28]]}}}