Evaluation of BCL6 and SIRT1 As Non-Invasive Diagnostic Markers of Endometriosis

Overview

Journal Curr Issues Mol Biol

Publisher MDPI

Specialty Molecular Biology

Date 2021 Oct 26

PMID 34698105

Citations 15

Authors

Alison M Sansone

Brooke V Hisrich

R Brandt Young

William F Abel

Zachary Bowens

Bailey B Blair

Avery T Funkhouser

David P Schammel

Lisa J Green

Bruce A Lessey

Anna V Blenda

Affiliations

Soon will be listed here.

Abstract

(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.

Citing Articles

BCL6 (B-cell lymphoma 6) expression in adenomyosis, leiomyomas and normal myometrium.

Salas L, Mielczarski B, Rivero R, da Cunha Filho J, Savaris R PLoS One. 2025; 20(2):e0317136.

PMID: 39903727 PMC: 11793761. DOI: 10.1371/journal.pone.0317136.

B Cell Lymphoma 6 (BCL6): A Conserved Regulator of Immunity and Beyond.

Liongue C, Almohaisen F, Ward A Int J Mol Sci. 2024; 25(20).

PMID: 39456751 PMC: 11507070. DOI: 10.3390/ijms252010968.

Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility.

Podgrajsek R, Ban Frangez H, Stimpfel M Int J Mol Sci. 2024; 25(7).

PMID: 38612425 PMC: 11011890. DOI: 10.3390/ijms25073613.

Potential biomarkers to predict return to fertility after discontinuation of female contraceptives-looking to the future.

Cordova-Gomez A, Wong A, Sims L, Doncel G, Dorflinger L Front Reprod Health. 2023; 5:1210083.

PMID: 37674657 PMC: 10477712. DOI: 10.3389/frph.2023.1210083.

How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis.

Sobstyl A, Chalupnik A, Mertowska P, Grywalska E Int J Mol Sci. 2023; 24(13).

PMID: 37446108 PMC: 10341671. DOI: 10.3390/ijms241310920.

References

Allman D, Jain A, Dent A, Maile R, Selvaggi T, Kehry M . BCL-6 expression during B-cell activation. Blood. 1996; 87(12):5257-68. View

Lin Z, Fang D . The Roles of SIRT1 in Cancer. Genes Cancer. 2013; 4(3-4):97-104. PMC: 3764469. DOI: 10.1177/1947601912475079. View

Soliman A, Surrey E, Bonafede M, Nelson J, Castelli-Haley J . Real-World Evaluation of Direct and Indirect Economic Burden Among Endometriosis Patients in the United States. Adv Ther. 2018; 35(3):408-423. PMC: 5859693. DOI: 10.1007/s12325-018-0667-3. View

Pasqualucci L, Migliazza A, Basso K, Houldsworth J, Chaganti R, Dalla-Favera R . Mutations of the BCL6 proto-oncogene disrupt its negative autoregulation in diffuse large B-cell lymphoma. Blood. 2003; 101(8):2914-23. DOI: 10.1182/blood-2002-11-3387. View

Buyalos R, Funari V, Azziz R, Watson J, Martinez-Maza O . Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. Fertil Steril. 1992; 58(2):302-6. View

Arima M, Fukuda T, Tokuhisa T . Role of the Transcriptional Repressor BCL6 in Allergic Response and Inflammation. World Allergy Organ J. 2013; 1(7):115-22. PMC: 3651038. DOI: 10.1097/WOX.0b013e31817dc522. View

Patel B, Rudnicki M, Yu J, Shu Y, Taylor R . Progesterone resistance in endometriosis: origins, consequences and interventions. Acta Obstet Gynecol Scand. 2017; 96(6):623-632. DOI: 10.1111/aogs.13156. View

Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I . The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres. Hum Reprod. 2012; 27(5):1292-9. DOI: 10.1093/humrep/des073. View

Basso K, Dalla-Favera R . BCL6: master regulator of the germinal center reaction and key oncogene in B cell lymphomagenesis. Adv Immunol. 2010; 105:193-210. DOI: 10.1016/S0065-2776(10)05007-8. View

10.

Gaben A, Saucier C, Bedin M, Redeuilh G, Mester J . 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. Mol Endocrinol. 2004; 18(11):2700-13. DOI: 10.1210/me.2003-0133. View

11.

Langley E, Pearson M, Faretta M, Bauer U, Frye R, Minucci S . Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002; 21(10):2383-96. PMC: 126010. DOI: 10.1093/emboj/21.10.2383. View

12.

Chantalat E, Valera M, Vaysse C, Noirrit E, Rusidze M, Weyl A . Estrogen Receptors and Endometriosis. Int J Mol Sci. 2020; 21(8). PMC: 7215544. DOI: 10.3390/ijms21082815. View

13.

Kennedy B, Smith E, Kaeberlein M . The enigmatic role of Sir2 in aging. Cell. 2005; 123(4):548-50. DOI: 10.1016/j.cell.2005.11.002. View

14.

Rezk N, Lashin M, Sabbah N . MiRNA 34-a regulate SIRT-1 and Foxo-1 expression in endometriosis. Noncoding RNA Res. 2021; 6(1):35-41. PMC: 7905260. DOI: 10.1016/j.ncrna.2021.02.002. View

15.

Carter J . Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc. 1994; 2(1):43-7. DOI: 10.1016/s1074-3804(05)80830-8. View

16.

Arguni E, Arima M, Tsuruoka N, Sakamoto A, Hatano M, Tokuhisa T . JunD/AP-1 and STAT3 are the major enhancer molecules for high Bcl6 expression in germinal center B cells. Int Immunol. 2006; 18(7):1079-89. DOI: 10.1093/intimm/dxl041. View

17.

Sinclair D, Guarente L . Unlocking the secrets of longevity genes. Sci Am. 2006; 294(3):48-51, 54-7. DOI: 10.1038/scientificamerican0306-48. View

18.

Giudice L, Kao L . Endometriosis. Lancet. 2004; 364(9447):1789-99. DOI: 10.1016/S0140-6736(04)17403-5. View

19.

Marjoribanks J, Ayeleke R, Farquhar C, Proctor M . Nonsteroidal anti-inflammatory drugs for dysmenorrhoea. Cochrane Database Syst Rev. 2015; (7):CD001751. PMC: 6953236. DOI: 10.1002/14651858.CD001751.pub3. View

20.

Chang C, Ye B, Chaganti R, Dalla-Favera R . BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor. Proc Natl Acad Sci U S A. 1996; 93(14):6947-52. PMC: 38914. DOI: 10.1073/pnas.93.14.6947. View