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. 2021 Sep 28;43(3):1350-1360.
doi: 10.3390/cimb43030096.

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

Alison M Sansone  1 , Brooke V Hisrich  1 , R Brandt Young  1 , William F Abel  1 , Zachary Bowens  2 , Bailey B Blair  1 , Avery T Funkhouser  1 , David P Schammel  3 , Lisa J Green  2 , Bruce A Lessey  4 , Anna V Blenda  1
Affiliations

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

Alison M Sansone et al. Curr Issues Mol Biol. .

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.

Keywords: BCL6; ELISA; SIRT1; biomarker; endometriosis; infertility; laparoscopic surgery; non-invasive.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Current limitations of endometriosis diagnosis and anticipated improvement with the development and use of reliable non-invasive testing.
Figure 2
Figure 2
Role of SIRT1 and BCL6 in Endometriosis. Increases in inflammatory responses, such the inflammatory cytokine IL-6, activates the oncogene KRAS to induce both SIRT1 and BCL6 production. SIRT1 and BCL6 are both thought to interfere with progesterone signaling, leading to progesterone resistance and estrogen dominance leading to endometriosis proliferation as described in Yoo (2017) and Marquardt (2019). BCL6, B-Cell Lymphoma 6 protein; ESR1, Estrogen Receptor 1; IL-6, Interleukin 6; KRAS, Kirsten Rat Sarcoma Viral Oncogene Homolog; P4, Progesterone; PGR, Progesterone Receptor; SIRT1, Sirtuin 1.
Figure 3
Figure 3
Comparison of Serum Concentrations of BCL6. No statistically significant difference is observed in the serum levels of BCL6 in healthy individuals compared to patients with I/II or III/IV Endometriosis. The “Control” group is patients with no endometriosis. The groups “Stage I/II” and “Stage III/IV” contained samples with stages I or II and stages III or IV endometriosis, respectively (ns = not significant).
Figure 4
Figure 4
Comparison of Serum Concentrations of SIRT1. A statistically significant difference is observed in the serum levels of SIRT1 in stage III/IV endometriosis patients compared to stage I/II endometriosis patients and healthy individuals. The groups “Stage I/II” and “Stage III/IV” contained samples with stages I or II and stages III or IV endometriosis, respectively. There was a statistically significant difference between the group “Stage I/II” and “Stage III/IV” with a p-value of 0.0038. There was also a statistically significant difference between the “Control” and “Stage III/IV” with a p-value of 0.0152. (ns = not significant, * p ≤ 0.05, ** p ≤ 0.01).
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