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Arsalan HM, Mumtaz H, Lagana AS. Biomarkers of endometriosis. Adv Clin Chem 2025; 126:73-120. [PMID: 40185537 DOI: 10.1016/bs.acc.2025.01.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2025]
Abstract
Endometriosis represents a diverse disease characterized by three distinct phenotypes: superficial peritoneal lesions, ovarian endometriomas, and deep infiltrating endometriosis. The most widely accepted pathophysiological hypothesis for endometriosis is rooted in retrograde menstruation, a phenomenon observed in most patients. Endometriosis is closely linked to infertility, but having endometriosis does not necessarily imply infertility. The disease can impact fertility through various mechanisms affecting the pelvic cavity, ovaries, and the uterus itself. MicroRNAs (miRNAs) indeed represent a fascinating and essential component of the regulatory machinery within cells. Discovered in the early 1990s, miRNAs have since been identified as critical players in gene expression control. Unfortunately, ovarian endometrioma is a common gynecologic disorder for which specific serum markers are currently lacking. Some have examined urocortin for its ability to differentiate endometriomas from other benign ovarian cysts. Another potential marker, Cancer Antigen 125 (CA-125) is a well-established indicator for epithelial cell ovarian cancer and its levels can be elevated in conditions such as endometriosis. CA-125 is derived from coelomic epithelia, including the endometrium, fallopian tube, ovary, and peritoneum. In this review we examine the pathophysiologic basis for endometriosis and highlight potential markers to more fully characterize the underlying biochemical processes linked to this multifaceted disease state.
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Affiliation(s)
- Hafiz Muhammad Arsalan
- Faculty of General Medicine, Altamimi International Medical University, Bishkek, Kyrgyzstan.
| | - Hina Mumtaz
- Department of Biochemistry, University of Central Punjab, Lahore, Pakistan.
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Nezhat CR, Oskotsky TT, Robinson JF, Fisher SJ, Tsuei A, Liu B, Irwin JC, Gaudilliere B, Sirota M, Stevenson DK, Giudice LC. Real world perspectives on endometriosis disease phenotyping through surgery, omics, health data, and artificial intelligence. NPJ WOMEN'S HEALTH 2025; 3:8. [PMID: 39926583 PMCID: PMC11802455 DOI: 10.1038/s44294-024-00052-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2024] [Accepted: 12/31/2024] [Indexed: 02/11/2025]
Abstract
Endometriosis is an enigmatic disease whose diagnosis and management are being transformed through innovative surgical, molecular, and computational technologies. Integrating single-cell and other omic disease data with clinical and surgical metadata can identify multiple disease subtypes with translation to novel diagnostics and therapeutics. Herein, we present real-world perspectives on endometriosis and the importance of multidisciplinary collaboration in informing molecular, epidemiologic, and cell-specific data in the clinical and surgical contexts.
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Affiliation(s)
- Camran R. Nezhat
- Center for Special Minimally Invasive and Robotic Surgery, Camran Nezhat Institute, Stanford University Medical Center, University of California, San Francisco, Woodside, CA 94061 USA
| | - Tomiko T. Oskotsky
- Bakar Computational Health Sciences Institute, University of California San Francisco, 490 Illinois St, Floor 2, San Francisco, CA 94158 USA
| | - Joshua F. Robinson
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 513 Parnassus Ave, Rm. 1621, San Francisco, CA 94143 USA
| | - Susan J. Fisher
- Center for Reproductive Sciences, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 35 Medical Center Way, Box 0665, San Francisco, CA 94143 USA
| | - Angie Tsuei
- Center for Special Minimally Invasive and Robotic Surgery, Camran Nezhat Institute, Woodside, CA 94061 USA
| | - Binya Liu
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue Room 1600 HSE, San Francisco, CA 94143 USA
| | - Juan C. Irwin
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue Room 1600 HSE, San Francisco, CA 94143 USA
| | - Brice Gaudilliere
- Department of Anesthesiology, Pain, and Perioperative Medicine, and (courtesy) Pediatrics, Stanford University, 3174 Porter Dr, Palo Alto, CA 94304 USA
| | - Marina Sirota
- Bakar Computational Health Sciences Institute, University of California San Francisco, 490 Illinois St, Floor 2, San Francisco, CA 94158 USA
| | - David K. Stevenson
- Department of Pediatrics, Stanford University, 453 Quarry Rd, Palo Alto, CA 94304 USA
| | - Linda C. Giudice
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco, 513 Parnassus Avenue Room 1600 HSE, San Francisco, CA 94143 USA
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Ahsan F, Santoso B, Rahmawati NY, Alditia FN, Mufid AF, Sa'adi A, Dwiningsih SR, Tunjungseto A, Widyanugraha MYA. Differential Expression of Granulysin, MHC Class I-Related Chain A, and Perforin in Serum and Peritoneal Fluid: Immune Dysregulation in Endometriosis-Related Infertility. Immunol Invest 2025; 54:234-249. [PMID: 39589023 DOI: 10.1080/08820139.2024.2431847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
INTRODUCTION Endometriosis is a chronic inflammatory disease characterized by endometrial-like tissue outside the uterus. Molecules linked to natural killer (NK) and cytotoxic T cells, including granulysin (GNLY), MHC class I-related chain A (MICA), and perforin (PRF1) support immune surveillance, though their roles in endometriosis remain unclear. This study investigates the association of these molecules with clinical parameters in infertile women with endometriosis. METHODS Eighty-seven infertile women undergoing diagnostic laparoscopy were included: 44 with endometriosis and 43 with benign gynecologic disorders. Serum and peritoneal molecules were measured using ELISA. Statistical analyses compared groups and correlated immune markers with clinical parameters. RESULTS Endometriosis patients displayed significantly higher PRF1 levels in serum (p = .038) and peritoneal fluid (p = .002), particularly in late-stage disease. Serum and peritoneal PRF1 levels correlated positively with the rASRM adhesion scores. Elevated serum PRF1 was observed in ovarian endometrioma (p = .021). Peritoneal MICA was higher in late-stage endometriosis (p = .013). Serum MICA was elevated in the follicular phase compared to the luteal phase (p = .008). CONCLUSION Elevated PRF1 and MICA levels were associated with endometriosis severity, indicating their potential as biomarkers. Future studies should validate this finding and explore its therapeutic role in endometriosis.
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Affiliation(s)
- Fadhil Ahsan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Budi Santoso
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Nanda Yuli Rahmawati
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | | | - Alfin Firasy Mufid
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ashon Sa'adi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Sri Ratna Dwiningsih
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Arif Tunjungseto
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - M Y Ardianta Widyanugraha
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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Xie Y, Wang D, Zhang N, Yang Q. Correlation analysis of recurrent factors in borderline ovarian tumors undergoing fertility preservation surgery. Front Oncol 2025; 15:1488247. [PMID: 39911631 PMCID: PMC11794081 DOI: 10.3389/fonc.2025.1488247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 01/03/2025] [Indexed: 02/07/2025] Open
Abstract
Objective To explore the relapse - related factors of fertility preservation surgery for borderline ovarian tumors. Methods Patients of childbearing age who underwent fertility preservation surgery for borderline ovarian tumors in Sheng jing Hospital of China Medical University from April 20 1 8 to April 20 2 3 were selected. Clinical data were collected and their clinical characteristics were statistically analyzed. It is to explore the risk factors of postoperative recurrence. Results A total of 30 8 patients were included in this study, of which 1 was lost to follow - up and 47 relapsed (4 7/3 0 7, 15. 3 1%). The results of multivariate analysis showed that the pathological features of micro papillary structure, intra operative as cites, bilateral tumors, and the increased ratio of neu tro phil to lymphocyte before surgery are independent risk factors for the recurrence of borderline ovarian tumors. Conclusion The prognosis of women of childbearing age with borderline ovarian tumors undergoing conservation function surgery is good. However, patients with high - risk recurrence factors should be paid special attention and closely followed up after surgery.
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Affiliation(s)
| | | | | | - Qing Yang
- Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
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Andrieu T, Duo A, Duempelmann L, Patzak M, Saner FAM, Skrabalova J, Donato C, Nestorov P, Mueller MD. Single-Cell RNA Sequencing of PBMCs Identified Junction Plakoglobin (JUP) as Stratification Biomarker for Endometriosis. Int J Mol Sci 2024; 25:13071. [PMID: 39684780 DOI: 10.3390/ijms252313071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/29/2024] [Accepted: 11/29/2024] [Indexed: 12/18/2024] Open
Abstract
This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16+ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14+/CD16+ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP's potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis.
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Affiliation(s)
- Thomas Andrieu
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
| | - Angelo Duo
- Scailyte AG, True Precision Medicine Through Single-Cell Science, Lichtstrasse 35, 4056 Basel, Switzerland
| | - Lea Duempelmann
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
| | - Magdalena Patzak
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
| | - Flurina Annacarina Maria Saner
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
| | - Jitka Skrabalova
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
| | - Cinzia Donato
- Scailyte AG, True Precision Medicine Through Single-Cell Science, Lichtstrasse 35, 4056 Basel, Switzerland
| | - Peter Nestorov
- Scailyte AG, True Precision Medicine Through Single-Cell Science, Lichtstrasse 35, 4056 Basel, Switzerland
| | - Michael D Mueller
- Endometriosis & Gynaecological Oncology Laboratory (EndoGO), Department for Biomedical Research (DBMR), University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland
- Inselspital Universitätsspital Bern, Women's Hospital-Universitätsklinik für Frauenheilkunde, Friedbühlstrasse 19, 3010 Bern, Switzerland
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Encalada Soto D. Navigating towards precision: evaluating the clinical value of non-invasive biomarkers for the diagnosis of endometriosis. Minerva Obstet Gynecol 2024; 76:564-577. [PMID: 38576337 DOI: 10.23736/s2724-606x.23.05313-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/06/2024]
Abstract
INTRODUCTION Endometriosis is a chronic disease that affects millions of women worldwide, causing dysmenorrhea, chronic pain, and infertility, and has a significant impact on the healthcare system. Despite efforts to understand its pathogenesis, endometriosis is a disease with heterogeneous presentations and phenotypes which is manifested in part by the lack of a non-invasive biomarker available for its diagnosis. This review aims to bridge the gap between theory and practice by summarizing the most promising areas of study for developing a reliable biomarker or combination of biomarkers for the non-invasive diagnosis of endometriosis. EVIDENCE ACQUISITION We conducted a comprehensive literature search using the electronic databases PubMed and MEDLINE. EVIDENCE SYNTHESIS This review summarizes the potential biomarkers for endometriosis, including glycoproteins, inflammatory markers, immunologic markers, angiogenic cytokines, micro RNAs and the microbiome. Each of these biomarkers' role in the development and progression of endometriosis, and their diagnostic potential are discussed in detail. CONCLUSIONS Endometriosis is a complex and underdiagnosed disease with significant health impact. The development of non-invasive biomarkers for its diagnosis would be immensely valuable, and promising research is being done in this area. While no single biomarker has yet emerged as a reliable diagnostic tool, this review highlights the potential of several biomarkers and the importance of continued research in this field. By improving the diagnosis of endometriosis, we can improve the lives of millions of women worldwide.
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Affiliation(s)
- Diana Encalada Soto
- Division of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, University of South Florida, Tampa, FL, USA -
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Wang S, Cheng H, Zhu H, Yu X, Ye X, Chang X. Precise capture of circulating endometrial cells in endometriosis. Chin Med J (Engl) 2024; 137:1715-1723. [PMID: 38679794 PMCID: PMC11268826 DOI: 10.1097/cm9.0000000000002910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM. METHODS Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients ( n = 34) hospitalized in the Peking University People's Hospital. We used the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarified the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. RESULTS The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 μm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage. CONCLUSION The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.
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Affiliation(s)
- Shang Wang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
| | - Hongyan Cheng
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
| | - Honglan Zhu
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
| | - Xiaoming Yu
- Reproductive Medicine Center, Peking University People's Hospital, Beijing 100044, China
| | - Xue Ye
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
| | - Xiaohong Chang
- Department of Obstetrics and Gynecology, Peking University People's Hospital, Beijing 100044, China
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Lee JK, Han K, Choi E, Baek J, Kim HR, Kim MD, Kim H, Seo SK. Effect of catheter-directed ethanol sclerotherapy on ovarian reserve in patients with recurrent endometrioma: comparative analysis with primary endometriosis. Eur Radiol 2024; 34:3298-3308. [PMID: 37848771 DOI: 10.1007/s00330-023-10320-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 08/28/2023] [Accepted: 09/15/2023] [Indexed: 10/19/2023]
Abstract
OBJECTIVE Catheter-directed ethanol sclerotherapy (CDS) is known to less affect the ovarian function, with comparable efficacy. This study aims to investigate the change in ovarian reserve after catheter-directed ethanol sclerotherapy in patients with recurrent endometrioma, as compared to primary endometrioma. MATERIALS AND METHODS Retrospective, observational study. Electronic medical records and images of patients with endometrioma who underwent CDS from August 2014 to April 2022 at a single institution were obtained. Patients aged > 18 years old and with anti-Müllerian hormone (AMH) level between 0.8 and 10.0 with regular menstruation were enrolled. Cyst diameter, laterality, AMH level, and CA-125 level before and after 1 month, 6 months, 1 year, 2 years, and 3 years of sclerotherapy were obtained. RESULTS A total of 180 patients were fit for analysis. There was no statistical difference in age and cyst size between the two groups. Mean values of AMH in each group were 3.35 in the primary group and 3.00 in the recurrent group prior to the procedure (p = 0.347). There was no significant difference in delta value of AMH after sclerotherapy in both groups at each follow-up period. Also, this result was consistent when stratified by laterality, preprocedural AMH level, and initial size of endometrioma. No case of recurrence was reported in both groups. CONCLUSIONS The effect of CDS on ovarian reserve is not inferior in recurrent endometrioma compared to primary endometrioma. Since sclerotherapy is known to less deteriorate the ovarian function than surgical removal of endometrioma, clinician could consider this as the first-line therapy in patients with recurrent endometrioma. CLINICAL RELEVANCE STATEMENT Catheter-directed ethanol sclerotherapy for patients with recurrent endometrioma has similar effect on ovarian reserve compared to patients with primary endometrioma. KEY POINTS • Secondary surgery for endometrioma has significant deleterious effect on ovarian function. • Catheter-directed sclerotherapy (CDS) for endometrioma had equally minimal adverse effect on ovarian reserve, represented as anti-Müllerian hormone (AMH), in both primary and recurrent groups. • Physicians should consider CDS for patients with recurrent endometrioma who desire to preserve ovarian function.
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Affiliation(s)
- Jae Kyung Lee
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Kichang Han
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Euna Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Jinkyung Baek
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Hae-Rim Kim
- College of Natural Science, School of Statistics, University of Seoul, 163, Seoulsiripdae-Ro, Dongdaemun-Gu, Seoul, 02504, South Korea
| | - Man-Deuk Kim
- Department of Radiology, Severance Hospital, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea
| | - Heeyon Kim
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
| | - Seok Kyo Seo
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
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Rahmawati NY, Ahsan F, Santoso B, Mufid AF, Sa'adi A, Dwiningsih SR, Tunjungseto A, Widyanugraha MYA. Soluble Factors CD14, CD163, and Migration Inhibitory Factor Are Associated with Endometriosis-Related Infertility. Gynecol Obstet Invest 2024; 89:335-345. [PMID: 38569489 DOI: 10.1159/000538525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Accepted: 03/19/2024] [Indexed: 04/05/2024]
Abstract
OBJECTIVES Myeloid cell-derived factors contribute to the immunopathology of endometriosis. Soluble CD14 (sCD14), CD163 (sCD163), and MIF serve as in vivo markers of myeloid function. However, these soluble molecules are largely unexplored in women with endometriosis-related infertility cases. We investigated three soluble markers, namely sCD14, sCD163, and MIF, in cases of infertility associated with endometriosis and correlated its level to the stage of endometriosis. DESIGN Eighty-seven women newly diagnosed with endometriosis or other benign gynecologic control cases linked to infertility were prospectively recruited and underwent diagnostic laparoscopy. PARTICIPANTS Forty-four patients with endometriosis were included in this study, comprising 19 patients with early-endometriosis (stages I and II) and 25 late-endometriosis (stages III and IV) based on the revised American Society for Reproductive Medicine (rASRM) classification. The remaining 43 patients constituted a control group with infertility due to other causes. METHODS The levels of sCD14, sCD163, and MIF in serum and peritoneal fluid were assessed using ELISA. RESULTS Endometriosis women exhibited significantly higher serum levels of sCD163 and MIF levels compared to the control group. Both sCD163 and MIF levels displayed a positive correlation with the rASRM adhesion score. Moreover, the MIF level in serum had a positive correlation with the rASRM endometriosis score. In receiver operating characteristic analysis, serum sCD163 and MIF could significantly discriminate endometriosis and non-endometriosis in infertility cases. LIMITATIONS Some limitations of the current study deserve to be underlined. First, the sensitive ELISA method was the sole-validated tool for detecting the markers in patient samples. Second, healthy or fertile women were not involved as the control group. CONCLUSIONS The elevated systemic levels of sCD163 and MIF correlated with the severity of endometriosis. These soluble molecules have a potential diagnostic capacity as a non-invasive biomarker. Furthermore, our data warrants future studies on the underlying mechanism of sCD163 and MIF in endometriosis-related infertility.
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Affiliation(s)
- Nanda Yuli Rahmawati
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Fadhil Ahsan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Budi Santoso
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Alfin Firasy Mufid
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Ashon Sa'adi
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Sri Ratna Dwiningsih
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - Arif Tunjungseto
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
| | - M Y Ardianta Widyanugraha
- Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
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10
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Dominoni M, Pasquali MF, Musacchi V, De Silvestri A, Mauri M, Ferretti VV, Gardella B. Neutrophil to lymphocytes ratio in deep infiltrating endometriosis as a new toll for clinical management. Sci Rep 2024; 14:7575. [PMID: 38555302 PMCID: PMC10981721 DOI: 10.1038/s41598-024-58115-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/25/2024] [Indexed: 04/02/2024] Open
Abstract
Several mechanisms, including altered local and systemic immune system, apoptosis, and new angiogenesis, are responsible for the development and progression of endometriosis. Over the years many markers have been studied, like CA 125 and, recently, neutrophil-to-lymphocyte ratio (NLR). This tool is cost-effectiveness and non-invasiveness as a marker of systemic inflammatory diseases. The aim of this study is to assess the role of NLR in the real-life management of patients with endometriosis in order to evaluate the possible association between this value and symptoms. We performed a retrospective analysis of 199 premenopausal women affected by endometriosis, from January 2013 to December 2020, evaluating the characteristics of disease, the symptoms and the NLR. Analyzing the neutrophiles, the mean ± SD value was 6.1 ± 4.5 × 103/ul, while for lymphocytes mean ± SD value was 1.8 ± 0.7.NLR was categorized according to its median value (> 2.62 vs ≤ 2.62). The comparison between NLR values and CA 125, endometriosis stage, dysmenorrhea and presence of chronic pelvic pain, adjusting for previous therapy did not find a significant association. An interesting result, although not significant, was the association between NLR and chronic pelvic pain (OR = 1.9). In the sub-group of patients without previous therapy this association is even stronger (OR = 4.8, 95% CI 0.5-50.2, p = 0.190). The link between NLR and chronic pelvic pain can provide a further hint to the clinician even when taking symptoms into account to develop a particular therapeutic treatment related to the various expressions of NLR. Finally, NLR may enable the creation of customized follow-up protocols that divide patients into high- and low-risk categories for endometriosis recurrence.
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Affiliation(s)
- Mattia Dominoni
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy.
- Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy.
| | - Marianna Francesca Pasquali
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy
- Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
| | - Valentina Musacchi
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy
- Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
| | - Annalisa De Silvestri
- SSD Biostatistica e Clinical Trial Center, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
| | - Matteo Mauri
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy
- Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
| | - Virginia Valeria Ferretti
- SSD Biostatistica e Clinical Trial Center, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
| | - Barbara Gardella
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100, Pavia, Italy
- Department of Obstetrics and Gynecology, IRCCS Fondazione Policlinico San Matteo, 27100, Pavia, Italy
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Zhang J, Wang J, Zhang J, Liu J, Xu Y, Zhu P, Dai L, Shu L, Liu J, Hou Z, Diao F, Liu J, Mao Y. Developing a Predictive Model for Minimal or Mild Endometriosis as a Clinical Screening Tool in Infertile Women: Uterosacral Tenderness as a Key Predictor. J Minim Invasive Gynecol 2024; 31:227-236. [PMID: 38147937 DOI: 10.1016/j.jmig.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 12/08/2023] [Accepted: 12/20/2023] [Indexed: 12/28/2023]
Abstract
STUDY OBJECTIVE To develop a noninvasive predictive model based on patients with infertility for identifying minimal or mild endometriosis. DESIGN A retrospective cohort study. SETTING This study was conducted at a tertiary referral center. PATIENTS A total of consecutive 1365 patients with infertility who underwent laparoscopy between January 2013 and August 2020 were divided into a training set (n = 910) for developing the predictive model and a validation set (n = 455) to confirm the model's prediction efficiency. The patients were randomly assigned in a 2:1 ratio. INTERVENTIONS Sensitivities, specificities, area under the curve, the Hosmer-Lemeshow goodness of fit test, Net Reclassification Improvement index, and Integrated Discrimination Improvement index were evaluated in the training set to select the optimum model. In the validation set, the model's discriminations, calibrations, and clinical use were tested for validation. MEASUREMENTS AND MAIN RESULTS In the training set, there were 587 patients with minimal or mild endometriosis and 323 patients without endometriosis. The combination of clinical parameters in the model was evaluated for both statistical and clinical significance. The best-performing model ultimately included body mass index, dysmenorrhea, dyspareunia, uterosacral tenderness, and serum cancer antigen 125 (CA-125). The nomogram based on this model demonstrated sensitivities of 87.7% and 93.3%, specificities of 68.6% and 66.4%, and area under the curve of 0.84 (95% confidence interval 0.81-0.87) and 0.85 (95% confidence interval 0.80-0.89) for the training and validation sets, respectively. Calibration curves and decision curve analyses also indicated that the model had good calibration and clinical value. Uterosacral tenderness emerged as the most valuable predictor. CONCLUSION This study successfully developed a predictive model with high accuracy in identifying infertile women with minimal or mild endometriosis based on clinical characteristics, signs, and cost-effective blood tests. This model would assist clinicians in screening infertile women for minimal or mild endometriosis, thereby facilitating early diagnosis and treatment.
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Affiliation(s)
- Jie Zhang
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Jing Wang
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Jingyi Zhang
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Jin Liu
- Clinical Research Institute of the First Affiliated Hospital of Nanjing Medical University (Dr. Jin Liu), Nanjing, China
| | - Yanhong Xu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Peipei Zhu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Lei Dai
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Li Shu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Jinyong Liu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Zhen Hou
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Feiyang Diao
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Jiayin Liu
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao)
| | - Yundong Mao
- State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University (Ms. Jie Zhang, Ms. Jingyi Zhang, Ms. Xu, Ms. Zhu, Mr. Dai, and Drs. Wang, Shu, Jinyong Liu, Hou, Diao, Jiayin Liu, and Mao).
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Chico-Sordo L, Ruiz-Martínez T, Toribio M, González-Martín R, Spagnolo E, Domínguez F, Hernández A, García-Velasco JA. Identification of miR-30c-5p microRNA in Serum as a Candidate Biomarker to Diagnose Endometriosis. Int J Mol Sci 2024; 25:1853. [PMID: 38339132 PMCID: PMC10855247 DOI: 10.3390/ijms25031853] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 01/30/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024] Open
Abstract
The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.
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Affiliation(s)
- Lucía Chico-Sordo
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (L.C.-S.); (F.D.); (J.A.G.-V.)
| | | | - Mónica Toribio
- IVIRMA Global Research Alliance, IVIRMA Madrid, 28023 Madrid, Spain
| | - Roberto González-Martín
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (L.C.-S.); (F.D.); (J.A.G.-V.)
| | - Emanuela Spagnolo
- Gynaecology Department, La Paz University Hospital, 28046 Madrid, Spain
| | - Francisco Domínguez
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (L.C.-S.); (F.D.); (J.A.G.-V.)
| | - Alicia Hernández
- Gynaecology Department, La Paz University Hospital, 28046 Madrid, Spain
| | - Juan A. García-Velasco
- IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain; (L.C.-S.); (F.D.); (J.A.G.-V.)
- IVIRMA Global Research Alliance, IVIRMA Madrid, 28023 Madrid, Spain
- School of Health Sciences, Medical Specialties and Public Health, Obstetrics and Gynecology Area, Rey Juan Carlos University Alcorcón, 28922 Madrid, Spain
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Shi H, Liu L, Deng X, Xing X, Zhang Y, Djouda Rebecca Y, Han L. Exosomal biomarkers in the differential diagnosis of ovarian tumors: the emerging roles of CA125, HE4, and C5a. J Ovarian Res 2024; 17:4. [PMID: 38178252 PMCID: PMC10768525 DOI: 10.1186/s13048-023-01336-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2023] [Accepted: 12/25/2023] [Indexed: 01/06/2024] Open
Abstract
OBJECTIVE Investigating the utility of serum exosomal markers CA125, HE4, and C5a, both individually and in combination, for distinguishing between benign and malignant ovarian tumors. METHODS In this study, we selected a total of 234 patients diagnosed with ovarian tumors, including 34 with malignant tumors, 10 with borderline ovarian tumors, and 190 with benign tumors. This study conducted comparisons of exosomal levels of CA125, HE4, and C5a among distinct groups, as well as making comparisons between serum and exosomal levels of CA125 and HE4. Furthermore, the diagnostic performance was assessed through Receiver Operating Characteristic (ROC) curve analysis. The Area Under the Curve (AUC) was computed, and a comparative evaluation of sensitivity and specificity was conducted to ascertain their effectiveness in determining the nature of ovarian tumors across different markers. RESULTS Serum CA125 and HE4 levels, the ROMA index, exosomal CA125, HE4, C5a levels, and their combined applied value (OCS value) were notably elevated in the ovarian non-benign tumor group compared to the benign tumor group, with statistical significance (P < 0.05). Exosomal and serum levels of CA125 and HE4 exhibited a positive correlation, with concentrations of these markers in serum surpassing those in exosomes. The combined OCS (AUC = 0.871) for CA125, HE4, and C5a in exosomes demonstrated superior sensitivity (0.773) and specificity (0.932) compared to serum tumor markers (CA125, HE4) and the ROMA index. The tumor stage represents an autonomous risk factor influencing the prognosis of individuals with ovarian malignancies. CONCLUSION The stage of ovarian malignancy is an independent risk factor for its prognosis. The combination of exosomal CA125, HE4 and C5a has a higher clinical value for the identification of the nature of ovarian tumours.
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Affiliation(s)
- Huihui Shi
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Liya Liu
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Xueli Deng
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Xiaoyu Xing
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Yan Zhang
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Yemeli Djouda Rebecca
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China
| | - Liping Han
- Department of Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou, 450000, China.
- , 1 East Jianshe Road, Zhengzhou, 450052, China.
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Burghaus S, Drazic P, Wölfler M, Mechsner S, Zeppernick M, Meinhold-Heerlein I, Mueller MD, Rothmund R, Vigano P, Becker CM, Zondervan KT, Beckmann MW, Fasching PA, Berner-Gatz S, Grünewald FS, Hund M, Kastner P, Klammer M, Laubender RP, Wegmeyer H, Wienhues-Thelen UH, Renner SP. Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study. Int J Gynaecol Obstet 2024; 164:305-314. [PMID: 37635683 DOI: 10.1002/ijgo.15062] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/29/2023]
Abstract
OBJECTIVE To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014-April 2018). METHODS This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18-45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were "pathologic symptomatic controls" or "pathology-free symptomatic controls". The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). RESULTS CA-125 performed best in "all endometriosis cases" versus "all symptomatic controls" (AUC 0.645, 95% confidence interval [CI] 0.600-0.690, q < 0.001) and increased (P < 0.001) with disease stage. In "all endometriosis cases" versus "pathology-free symptomatic controls", S100-A12 performed best (AUC 0.692, 95% CI 0.614-0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569-0.729, q = 0.021). In "adenomyosis only cases" versus "symptomatic controls" or "pathology-free symptomatic controls", respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551-0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611-0.792, q = 0.004). CONCLUSION This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.
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Affiliation(s)
- Stefanie Burghaus
- Department of Gynecology and Obstetrics, Erlangen University Hospital, University Endometriosis Center for Franconia, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Predrag Drazic
- Endometriosis Center, Ammerland Clinic GmbH, Westerstede, Germany
| | - Monika Wölfler
- Department of Gynecology and Obstetrics and Gynecology, Medical University, Graz, Austria
| | - Sylvia Mechsner
- Department of Gynecology, Endometriosis Research Center Charité, Charité University Hospital, Campus Virchow Klinikum, Berlin, Germany
| | - Magdalena Zeppernick
- Department of Gynecology and Obstetrics, RWTH Aachen University Hospital, Aachen, Germany
- Department of Gynecology and Obstetrics, Justus Liebig University, Giessen, Germany
| | - Ivo Meinhold-Heerlein
- Department of Gynecology and Obstetrics, RWTH Aachen University Hospital, Aachen, Germany
- Department of Gynecology and Obstetrics, Justus Liebig University, Giessen, Germany
| | - Michael D Mueller
- Department of Obstetrics and Gynecology, Inselspital, University of Bern, Bern, Switzerland
| | - Ralf Rothmund
- Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany
| | - Paola Vigano
- Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Italy
| | - Christian M Becker
- Oxford Endometriosis Care and Research (CaRe) Centre, Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK
| | - Krina T Zondervan
- Oxford Endometriosis Care and Research (CaRe) Centre, Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, UK
- Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK
| | - Matthias W Beckmann
- Department of Gynecology and Obstetrics, Erlangen University Hospital, University Endometriosis Center for Franconia, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | - Peter A Fasching
- Department of Gynecology and Obstetrics, Erlangen University Hospital, University Endometriosis Center for Franconia, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| | | | | | - Martin Hund
- Roche Diagnostics International Ltd, Rotkreuz, Switzerland
| | | | | | | | | | | | - Stefan P Renner
- Department of Gynecology and Obstetrics, Erlangen University Hospital, University Endometriosis Center for Franconia, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
- Department of Gynecology and Obstetrics, Hospital Böblingen, Klinikverbund-Suedwest, Klinikum Sindelfingen-Böblingen, Böblingen, Germany
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Ji S, Liu Y, Yan L, Zhang Y, Li Y, Zhu Q, Xia W, Ge S, Zhang J. DIA-based analysis of the menstrual blood proteome identifies association between CXCL5 and IL1RN and endometriosis. J Proteomics 2023; 289:104995. [PMID: 37657716 DOI: 10.1016/j.jprot.2023.104995] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 07/23/2023] [Accepted: 08/18/2023] [Indexed: 09/03/2023]
Abstract
Endometriosis is a gynecological disease related to menstruation that affects nearly 10% of reproductive-age women. However, so far, there are no reliable diagnostic biomarkers for endometriosis, causing a delay in diagnosis of 6.7 ± 6.2 years. Menstrual blood is a non-invasive source of endometrial tissue that can be analyzed for biomarkers of endometriosis. In this study, menstrual blood samples were collected from women with (n = 8) and without (n = 8) endometriosis. Data Independent Acquisition (DIA)-based mass spectrometry and bioinformatic analysis were used to quantify and identify differentially expressed proteins (DEPs) using the thresholds of fold change >1.5 and P value <0.05. A total of 95 DEPs were identified in menstrual blood from women with endometriosis compared to women without endometriosis, of which 64 were up-regulated and 31 were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to functionally annotate DEPs. Protein-protein interaction (PPI) network analysis was then conducted to identify hub genes and the MCODE plugin placed CXCL1, CXCL3, CXCL5, CCL18, and IL1RN in the most significant cluster network. The expression of the above candidate proteins was confirmed by enzyme-linked immunosorbent assay (ELISA), among which CXCL5 and IL1RN protein expression was increased in patients with endometriosis, indicating that CXCL5 and IL1RN in menstrual blood may be useful biomarkers to diagnose endometriosis from non-invasive samples. SIGNIFICANCE: Endometriosis is a common gynecological disease that causes discomfort in many women. Unfortunately, the diagnosis of endometriosis is frequently delayed due to a lack of reliable non-invasive biomarkers. To our knowledge, this is the first time that DIA-MS was used to characterize the proteome and identify the differentially expressed proteins in menstrual blood from women with endometriosis. The results, as confirmed by ELISA, showed that CXCL5 and IL1RN protein expression is significantly increased in patients with endometriosis, indicating that these proteins can be used as biomarkers for endometriosis. This study contributes to the identification of putative endometriosis biomarkers from non-invasive samples and lays the groundwork for future research into the roles of CXCL5 and IL1RN in the pathogenesis of endometriosis.
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Affiliation(s)
- Sifan Ji
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yuan Liu
- Department of Pathology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China
| | - Li Yan
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yiqin Zhang
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Yamei Li
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Qian Zhu
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Wei Xia
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China
| | - Shunna Ge
- Department of Central Laboratory, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
| | - Jian Zhang
- Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No. 910, Hengshan Rd, Shanghai 200030, China; Shanghai Municipal Key Clinical Specialty, Shanghai 200030, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China.
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Keum J, Lee WM, Choi JS, Bae J, Cho S, Kang BK. Diagnostic Clues for Women with Acute Surgical Abdomen Associated with Ruptured Endometrioma. J Pers Med 2023; 13:1226. [PMID: 37623476 PMCID: PMC10455920 DOI: 10.3390/jpm13081226] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/23/2023] [Accepted: 07/31/2023] [Indexed: 08/26/2023] Open
Abstract
(1) Background: An investigation of the preoperative diagnostic clues used to identify ruptured endometrioma by comparing the ruptured and unruptured states in patients who underwent laparoscopic operations due to endometrioma. (2) Methods: Patients with ruptured endometriomas (14 patients) and unruptured endometriomas (60 patients) were included, and clinical symptoms, laboratory findings, and radiological findings were analyzed. (3) Results: There were no significant differences in age, parity, last menstrual cycle days, or median size of endometrioma between two groups (group A: ruptured; group B: unruptured). The median serum level of CA 125 was 345.1 U/mL in group A and 49.8 U/mL in group B (p = 0.000). The median serum levels of CA 19-9 in group A and B were 46.0 U/mL and 19.1 U/mL, respectively (p = 0.005). The median serum level of CRP in group A was 1.2 g/dL, whereas it was 0.3 in group B (p = 0.000). ROC analysis showed that the optimal CA 125 cutoff value was 100.9 U/mL; the optimal CA 19-9 cutoff value was 27.7 U/mL; and the optimal CRP cutoff value was 1.0 g/dL. (4) Conclusions: Ruptured endometrioma can be diagnosed preoperatively using a combination of clinical symptoms, laboratory findings, and radiological findings. If a physician suspects a ruptured endometrioma, surgery should be performed to ensure optimal prognosis.
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Affiliation(s)
- Jihyun Keum
- Division of Gynecologic Oncology and Gynecologic Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; (J.K.); (J.S.C.); (J.B.); (S.C.)
| | - Won Moo Lee
- Division of Gynecologic Oncology and Gynecologic Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; (J.K.); (J.S.C.); (J.B.); (S.C.)
| | - Joong Sub Choi
- Division of Gynecologic Oncology and Gynecologic Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; (J.K.); (J.S.C.); (J.B.); (S.C.)
| | - Jaeman Bae
- Division of Gynecologic Oncology and Gynecologic Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; (J.K.); (J.S.C.); (J.B.); (S.C.)
| | - Seongsil Cho
- Division of Gynecologic Oncology and Gynecologic Minimally Invasive Surgery, Department of Obstetrics and Gynecology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea; (J.K.); (J.S.C.); (J.B.); (S.C.)
| | - Bo Kyeong Kang
- Department of Radiology, Hanyang University College of Medicine, Seoul 04763, Republic of Korea;
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Janša V, Pušić Novak M, Ban Frangež H, Rižner TL. TGFBI as a candidate biomarker for non-invasive diagnosis of early-stage endometriosis. Hum Reprod 2023; 38:1284-1296. [PMID: 37187159 PMCID: PMC10320490 DOI: 10.1093/humrep/dead091] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 04/16/2023] [Indexed: 05/17/2023] Open
Abstract
STUDY QUESTION Can cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) alone or in combination with cancer antigen 125 (CA-125) be considered as potential blood biomarkers of endometriosis? SUMMARY ANSWER The results of this study indicate that COMP has no diagnostic value. TGFBI has potential as a non-invasive biomarker of the early stages of endometriosis, while TGFBI together with CA-125 has similar diagnostic characteristics as CA-125 alone for all stages of endometriosis. WHAT IS KNOWN ALREADY Endometriosis is a common, chronic gynecological disease that significantly affects patient quality of life by causing pain and infertility. The gold standard for diagnosis is visual inspection of pelvic organs by laparoscopy, therefore there is an urgent need for discovery of non-invasive biomarkers for endometriosis to reduce diagnostic delays and allow earlier treatment of patients. The potential biomarkers for endometriosis evaluated in this study (COMP and TGFBI) were previously identified by our proteomic analysis of peritoneal fluid samples. STUDY DESIGN, SIZE, DURATION This is a case-control study divided into a discovery (n = 56 patients) and a validation phase (n = 237 patients). All patients were treated between 2008 and 2019 in a tertiary medical center. PARTICIPANTS/MATERIALS, SETTING, METHOD Patients were stratified based on the laparoscopic findings. The discovery phase included 32 endometriosis patients (cases) and 24 patients with confirmed absence of endometriosis (controls). The validation phase included 166 endometriosis and 71 control patients. Concentrations of COMP and TGFBI were measured by ELISA in plasma samples, whereas concentration of CA-125 was measured using a clinically validated assay for serum samples. Statistical and receiver operating characteristic (ROC) curve analyses were performed. The classification models were built using the linear support vector machine (SVM) method with the SVM built-in feature ranking method. MAIN RESULTS AND THE ROLE OF CHANCE The discovery phase revealed significantly increased concentration of TGFBI, but not COMP, in plasma samples of patients with endometriosis compared to controls. In this smaller cohort, univariate ROC analysis showed fair diagnostic potential of TGFBI, with an AUC value of 0.77, sensitivity of 58%, and specificity of 84%. The classification model built using linear SVM and combining TGFBI and CA-125 showed an AUC value of 0.91, sensitivity of 88% and specificity of 75% in distinguishing patients with endometriosis from controls. The validation phase results revealed similar diagnostic characteristics of the SVM model combining TGFBI and CA-125, with an AUC value of 0.83, sensitivity of 83% and specificity of 67% and CA-125 alone with AUC value of 0.83, sensitivity of 73% and specificity of 80%. TGFBI exhibited good diagnostic potential for early-stage endometriosis (revised American Society for Reproductive Medicine stage I-II), with an AUC value of 0.74, sensitivity of 61% and specificity of 83% compared to CA-125, which had an AUC value of 0.63, sensitivity of 60% and specificity of 67%. An SVM model combining TGFBI and CA-125 showed a high AUC value of 0.94 and sensitivity of 95% for diagnosing moderate-to-severe endometriosis. LIMITATIONS, REASONS FOR CAUTION The diagnostic models were built and validated from a single endometriosis center, and thus further validation and technical verification in a multicenter study with a larger cohort is needed. Additional limitation was lack of histological confirmation of disease for some patients in the validation phase. WIDER IMPLICATIONS OF THE FINDINGS This study revealed for the first time increased concentration of TGFBI in plasma samples of patients with endometriosis, particularly those with minimal-to-mild endometriosis, compared to controls. This is the first step in considering TGFBI as a potential non-invasive biomarker for the early stages of endometriosis. It also opens a path for new basic research to investigate the importance of TGFBI in the pathophysiology of endometriosis. Further studies are needed to confirm the diagnostic potential of a model based on TGFBI and CA-125 for the non-invasive diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The preparation of this manuscript was supported by grant J3-1755 from the Slovenian Research Agency to T.L.R and EU H2020-MSCA-RISE project TRENDO (grant 101008193). All authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER NCT0459154.
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Affiliation(s)
- Vid Janša
- Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Maja Pušić Novak
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Helena Ban Frangež
- Department of Obstetrics and Gynaecology, University Medical Centre Ljubljana, Ljubljana, Slovenia
- Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Tea Lanišnik Rižner
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Szubert M, Rycerz A, Wilczyński JR. How to Improve Non-Invasive Diagnosis of Endometriosis with Advanced Statistical Methods. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:499. [PMID: 36984500 PMCID: PMC10059817 DOI: 10.3390/medicina59030499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/26/2023] [Accepted: 02/28/2023] [Indexed: 03/06/2023]
Abstract
Background and Objectives: Endometriosis is one of the most common gynecological disorders in women of reproductive age. Causing pelvic pain and infertility, it is considered one of the most serious health problems, being responsible for work absences or productivity loss. Its diagnosis is often delayed because of the need for an invasive laparoscopic approach. Despite years of studies, no single marker for endometriosis has been discovered. The aim of this research was to find an algorithm based on symptoms and laboratory tests that could diagnose endometriosis in a non-invasive way. Materials and Methods: The research group consisted of 101 women hospitalized for diagnostic laparoscopy, among which 71 had confirmed endometriosis. Data on reproductive history were collected in detail. CA125 (cancer antigen-125) level and VEGF1(vascular endothelial growth factor 1) were tested in blood samples. Among the used statistical methods, the LASSO regression-a new important statistical tool eliminating the least useful features-was the only method to have significant results. Results: Out of 19 features based on results of LASSO, 7 variables were chosen: body mass index, age of menarche, cycle length, painful periods, information about using contraception, CA125, and VEGF1. After multivariate logistic regression with a backward strategy, the three most significant features were evaluated. The strongest impact on endometriosis prediction had information about painful periods, CA125 over 15 u/mL, and the lowest BMI, with a sensitivity of 0.8800 and a specificity of 0.8000, respectively. Conclusions: Advanced statistical methods are crucial when creating non-invasive tests for endometriosis. An algorithm based on three easy features, including painful menses, BMI level, and CA125 concentration could have an important place in the non-invasive diagnosis of endometriosis. If confirmed in a prospective study, implementing such an algorithm in populations with a high risk of endometriosis will allow us to cover patients suspected of endometriosis with proper treatment.
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Affiliation(s)
- Maria Szubert
- Department of Surgical and Oncological Gynecology, 1st Department of Gynecology and Obstetrics, Medical University of Lodz, M. Pirogow’s Teaching Hospital, Wilenska 37 St., 94-029 Lodz, Poland
- Club 35, Polish Society of Gynecologists and Obstetricians, ul. Cybernetyki 7F/87, 02-677 Warszawa, Poland
| | - Aleksander Rycerz
- Department of Surgical and Oncological Gynecology, 1st Department of Gynecology and Obstetrics, Medical University of Lodz, M. Pirogow’s Teaching Hospital, Wilenska 37 St., 94-029 Lodz, Poland
- Faculty of Mathematics and Computer Science, University of Lodz, Banacha 22, 90-238 Lodz, Poland
| | - Jacek R. Wilczyński
- Department of Surgical and Oncological Gynecology, 1st Department of Gynecology and Obstetrics, Medical University of Lodz, M. Pirogow’s Teaching Hospital, Wilenska 37 St., 94-029 Lodz, Poland
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Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Analysis in Endometriosis Patients: A Prospective Observational Translational Study. J Clin Med 2023; 12:jcm12030922. [PMID: 36769570 PMCID: PMC9918082 DOI: 10.3390/jcm12030922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 01/04/2023] [Accepted: 01/14/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Endometriosis affects women of reproductive age, and its pathogenesis is still unclear. Typically, it overlaps other similar medical and surgical conditions, determining a delay in early diagnosis. Metabolomics allows studying metabolic changes in different physiological or pathological states to discover new potential biomarkers. We used the gas chromatography-mass spectrometer (GC-MS) to explore metabolic alterations in endometriosis to better understand its pathophysiology and find new biomarkers. METHODS Twenty-two serum samples of patients with symptomatic endometriosis and ten without it were collected and subjected to GC-MS analysis. Multivariate and univariate statistical analyses were performed, followed by pathway analysis. RESULTS Partial least squares discriminant analysis was performed to determine the differences between the two groups (p = 0.003). Threonic acid, 3-hydroxybutyric acid, and proline increased significantly in endometriosis patients, while alanine and valine decreased. ROC curves were built to test the diagnostic power of metabolites. The pathway analysis identified the synthesis and degradation of ketone bodies and the biosynthesis of phenylalanine, tyrosine, and tryptophan as the most altered pathways. CONCLUSIONS The metabolomic approach identifies metabolic alterations in women with endometriosis. These findings may improve our understanding of the pathophysiological mechanisms of disease and the discovery of new biomarkers.
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Non-invasive diagnosis of endometriosis: Immunologic and genetic markers. Clin Chim Acta 2023; 538:70-86. [PMID: 36375526 DOI: 10.1016/j.cca.2022.11.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 11/07/2022] [Accepted: 11/07/2022] [Indexed: 11/13/2022]
Abstract
Endometriosis, a benign gynecologic and chronic inflammatory disease, is defined by the presence of endometrial tissue outside the uterus characterized mainly by pelvic pain and infertility. Because endometriosis affects approximately 10% of females, it represents a significant socioeconomic burden worldwide having tremendous impact on daily quality of life. Accurate and prompt diagnosis is crucial for the management of this debilitating disorder. Unfortunately, diagnosis is typically delayed to lack of specific symptoms and readily accessible biomarkers. Although histopathologic examination remains the current gold standard, this approach is highly invasive and not applicable for early screening. Recent work has focused on the identification of reliable biomarkers including immunologic, ie, immune cells, antibodies and cytokines, as well as genetic and biochemical markers, ie, microRNAs, lncRNAs, circulating and mitochondrial nucleic acids, along with some hormones, glycoproteins and signaling molecules. Confirmatory research studies are, however, needed to more fully establish these markers in the diagnosis, progression and staging of these endometrial lesions.
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Önal M, Karli P, Özdemir AZ, Kocaman A, Katirci Y, Çoban G, Nakişli GK, Civil Y, Avci B. Serum kisspeptin levels in deep-infiltrating, ovarian, and superficial endometriosis: A prospective observational study. Medicine (Baltimore) 2022; 101:e31529. [PMID: 36397399 PMCID: PMC9666188 DOI: 10.1097/md.0000000000031529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The diagnosis of endometriosis may delay for many years due to non-deterministic symptoms and avoiding surgical interventions. Kisspeptins are hormones that interact with endometrial tissue to limit invasions during placentation and various cancers and are suggested to be also associated with endometriosis. This study evaluated if serum kisspeptin levels are associated with the invasion depth in endometriosis. Forty patients between 18 and 45 years of age and admitted to a tertiary-care Obstetrics and Gynecology Department between 2020 and 2021 with a diagnosis of endometriosis, and 40 patients without endometrioma were included in the study. Demographic, obstetric, clinical, and biochemical characteristics were evaluated in patients with superficial (SE) and deep infiltrating (DIE) endometriosis and healthy controls. Twenty patients (50%) had SE, 14 (35%) had DIE, and 22 (55%) had endometrioma in the patient group. Fertility rates were higher among controls, but similar between patients with SE and DIE. CA125 levels were significantly higher in the DIE group. SE and DIE groups had similar kisspeptin values, significantly higher than controls. CA125 and kisspeptin levels were not correlated in study groups. Serum kisspeptin levels were significantly different between endometriosis patients and healthy controls. However, kisspeptin levels were unable to differentiate endometriosis severity. Our results suggest that kisspeptins might play a role in the pathogenesis of endometriosis, which needs further assessment in more comprehensive studies.
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Affiliation(s)
- Mesut Önal
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
- * Correspondence: Mesut Önal, Department of Gynecology and Obstetrics, Ondokuz Mayis University, Samsun 55200, Turkey (e-mail: )
| | - Pervin Karli
- Department of Gynecology and Obstetrics, Medical Park Hospital, Samsun, Turkey
| | - Ayşe Zehra Özdemir
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Adem Kocaman
- Department of Histology and Embryology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Yunus Katirci
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Gülnur Çoban
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Gülen Kübra Nakişli
- Department of Gynecology and Obstetrics, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Yeşim Civil
- Department of Histology and Embryology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
| | - Bahattin Avci
- Department of Biochemistry, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
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Senocak GNC, Yapca OE, Yılmaz EPT, Ozturk N, Ozdes S, Kumtepe Y. May endocan be a new biomarker in the diagnosis of endometriosis? J Gynecol Obstet Hum Reprod 2022; 51:102423. [DOI: 10.1016/j.jogoh.2022.102423] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/27/2022] [Accepted: 06/08/2022] [Indexed: 10/18/2022]
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Abstract
PURPOSE OF REVIEW Endometriosis is a complex benign gynaecologic condition with heterogenous presentations and a large impact on the global healthcare system and on the quality of life for millions of women. Currently, the gold standard for diagnosis involves direct visualization of lesions during surgery confirmed by histopathological diagnosis, resulting in an average delay in its initial diagnosis of 8-10 years. Therefore, the search for noninvasive diagnostic testing options has been subject to a large body of research. RECENT FINDINGS Multiple potential biomarkers have been explored for noninvasive testing for endometriosis, including glycoproteins, inflammatory cytokines, immunological molecules, angiogenesis markers, hormones, micro RNAs (miRNAs), proteomics, metabolomics, genomics and the microbiome. SUMMARY Although there are challenges to consider, areas for real promise and advancement in the noninvasive diagnosis of endometriosis are currently being explored with real promise in the area of miRNAs, proteomics, metabolomics, genomics and the microbiome.
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Lukács L, Kovács AR, Pál L, Szűcs S, Lampé R. Evaluating the Phagocytic Index of Peripheral Leukocytes in Endometriosis by Plasma Experiments. Medicina (B Aires) 2022; 58:medicina58070925. [PMID: 35888644 PMCID: PMC9316155 DOI: 10.3390/medicina58070925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 11/16/2022] Open
Abstract
Background and Objectives: Endometriosis is a benign, chronic disease, that negatively influences the quality of life of affected women and is responsible for a remarkable amount of infertility. The pathophysiology of the disease is still not clarified, but the insufficient immune surveillance plays a significant role in it. The phagocyte function of innate immune cells may play a role in the elimination of ectopic endometrium. The purpose of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes, incubated in heat-inactivated and not-inactivated plasma samples from healthy women and from women with endometriosis before and after the surgical treatment. Materials and Methods: Blood samples were collected from eight preoperative and eight postoperative patients with endometriosis before and after the surgical treatment, and from 16 healthy patients as controls. Neutrophil granulocytes, monocytes and blood plasma samples were isolated. Cells were incubated in different plasma samples, and the phagocytic index was determined with a fluorescence microscope. Results: The phagocytic index of granulocytes and monocytes isolated from patients with endometriosis was significantly decreased compared to healthy women after the cells were incubated in their own plasma. Preoperatively isolated cells from patients with endometriosis demonstrated an improved phagocyte function after incubating them in plasma samples from healthy controls. In contrast, the phagocytic activity of cells from healthy women significantly reduced after being incubated in the plasma of preoperative endometriosis patients. The heat-inactivation of plasma samples did not affect the results. Conclusions: Active endometriosis lesions may produce heat-stable systemic immunomodulatory factors, which reduced the phagocyte function of peripheral monocytes and neutrophil granulocytes. The phagocyte function of these cells can be normalized after the complete surgical removal of endometriosis, which then demonstrates similar values as in healthy women.
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Affiliation(s)
- Luca Lukács
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 4031 Debrecen, Hungary; (L.L.); (A.R.K.)
| | - Anna Rebeka Kovács
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 4031 Debrecen, Hungary; (L.L.); (A.R.K.)
| | - László Pál
- Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4028 Debrecen, Hungary; (L.P.); (S.S.)
| | - Sándor Szűcs
- Department of Public Health and Epidemiology, Faculty of Medicine, University of Debrecen, 4028 Debrecen, Hungary; (L.P.); (S.S.)
| | - Rudolf Lampé
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, 4031 Debrecen, Hungary; (L.L.); (A.R.K.)
- Correspondence:
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25
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Kusum K, Raj R, Rai S, Pranjali P, Ashish A, Vicente-Muñoz S, Chaube R, Kumar D. Elevated Circulatory Proline to Glutamine Ratio (PQR) in Endometriosis and Its Potential as a Diagnostic Biomarker. ACS OMEGA 2022; 7:14856-14866. [PMID: 35557708 PMCID: PMC9088897 DOI: 10.1021/acsomega.2c00332] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 04/01/2022] [Indexed: 06/15/2023]
Abstract
Endometriosis (EM) is a hormone-dependent gynecological disease associated with chronic pelvic pain and altered immuno-inflammatory processes. It shares some cancer-like characteristics such as increased proline biosynthesis and activated glutaminolysis. Both proline and glutamine are interconvertible metabolically, and studies have shown their roles in cancer cell metabolic reprogramming, redox homeostasis, occurrence/development of endometrial carcinoma, and its further progression toward the malignant state. So based on this, we hypothesized that the circulatory proline to glutamine ratio (PQR) would be altered in EM and may serve as an indicative biomarker to improve the clinical diagnosis of EM. In present study, the circulatory-PQR levels were estimated for 39 EM patients and 48 age matched healthy female subjects using 800 MHz NMR spectroscopy. Among 39 EM patients, 15 were in the clinical stages I to II and referred to here as moderate EM (MEM) patients and 24 were in the clinical stages III to IV and referred here as severe EM (SEM) patients. The circulatory-PQR levels were significantly increased in EM patients (0.99 ± 0.13 μM in MEM; 1.39 ± 0.22 μM in SEM) compared to normal control (NC) subjects (0.52 ± 0.05 μM in NC). Further, the circulatory PQR levels exhibit the highest diagnostic potential with area under receiver operating characteristic (AUROC) curve values equal to 0.87 ± 0.04 [95%CI = 0.79-0.96] for MEM and 0.89 ± 0.04 [95% CI = 0.82-0.96] for SEM. These results suggested that circulatory-PQR has significant potential to serve as a noninvasive biomarker for diagnostic/prognostic screening of EM and further underscored the importance of these two nonessential amino acids (proline and glutamine) in cancer metabolism.
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Affiliation(s)
- Kusum Kusum
- Department
of Zoology, Institute of Science, Banaras
Hindu University, Varanasi-221005, Uttar Pradesh, India
| | - Ritu Raj
- Centre
of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow-226014, Uttar Pradesh, India
| | - Sangeeta Rai
- Department
of Obstetrics and Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India
| | - Pranjali Pranjali
- Centre
of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow-226014, Uttar Pradesh, India
| | - Ashish Ashish
- Department
of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India
| | - Sara Vicente-Muñoz
- NMR-Metabolomics
Core, Division of Pathology, Cincinnati
Children’s Hospital Medical Center, Cincinnati, Ohio 45229, United States
| | - Radha Chaube
- Department
of Zoology, Institute of Science, Banaras
Hindu University, Varanasi-221005, Uttar Pradesh, India
| | - Dinesh Kumar
- Centre
of Biomedical Research (CBMR), SGPGIMS Campus, Lucknow-226014, Uttar Pradesh, India
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Diagnostic use of CA 125 values measured on the 2nd and 14th days of the menstrual cycle in endometriosis. JOURNAL OF SURGERY AND MEDICINE 2022. [DOI: 10.28982/josam.988164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Akhmaltdinova L, Appazova L, Turdybekova Y, Kopobayeva I, Amirbekova Z, Marinkin I. Serum Level of Ligand Programmed Death-1 in Endometriosis. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.8733] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
AIM: In this study, is to evaluate serum level of ligand programmed death-1 (PDL1) in patients with genital endometriosis.
MATERIAL AND METHODS: For PDL-1, cancer antigen 125 (CA 125), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) determination, venous blood was taken 1 h before surgery and/or treatment. All patients were stratified by the presence or absence of endometriosis according to the American Society of Reproductive Medicine’s Revised Classification of Endometriosis of the American Society of Reproductive Medicine.
RESULTS: Twenty-one patients with endometriosis participated in the study. The PDL-1 level an experienced group was 55.32 ng/ml (interquartile range [IQR] 34.53–76.20); in the control group was 19.72 ng/ml (IQR 14.72–24.78), which was a statistically significant decrease (p < 0.001). A significant increase in CA125 31.87 (IQR 15.43–36.96) was detected (p < 0.001). In the experimental group, all pro-inflammatory cytokines were elevated (IL-6, IL-8, and TNF, p < 0.013; <0.001; and <0.001) and almost twice increased VEGF 243.44 (IQR 194.56–328.07), (p = 0.016). A noticeable correlation was found between the following indicators PDL-1-CA125, PDL-1-IL-8, and PDL-1-TNF, and a moderate correlation was found between PDL-1 and VEFF (p = 0.006).
CONCLUSIONS: The results of the study showed that the levels of PDL-1, CA 125, IL-6, IL-8, TNF, and VEGF were statistically significantly different in the experimental and control groups, and a correlation was also revealed between the levels of PDL-1 and CA125, IL-8 and TNF in patients with genital endometriosis. Therefore, further studies with larger numbers of patients are required.
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Becker CM, Bokor A, Heikinheimo O, Horne A, Jansen F, Kiesel L, King K, Kvaskoff M, Nap A, Petersen K, Saridogan E, Tomassetti C, van Hanegem N, Vulliemoz N, Vermeulen N. ESHRE guideline: endometriosis. Hum Reprod Open 2022; 2022:hoac009. [PMID: 35350465 PMCID: PMC8951218 DOI: 10.1093/hropen/hoac009] [Citation(s) in RCA: 604] [Impact Index Per Article: 201.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Indexed: 12/14/2022] Open
Abstract
STUDY QUESTION How should endometriosis be diagnosed and managed based on the best available evidence from published literature? SUMMARY ANSWER The current guideline provides 109 recommendations on diagnosis, treatments for pain and infertility, management of disease recurrence, asymptomatic or extrapelvic disease, endometriosis in adolescents and postmenopausal women, prevention and the association with cancer. WHAT IS KNOWN ALREADY Endometriosis is a chronic condition with a plethora of presentations in terms of not only the occurrence of lesions, but also the presence of signs and symptoms. The most important symptoms include pain and infertility. STUDY DESIGN SIZE DURATION The guideline was developed according to the structured methodology for development of ESHRE guidelines. After formulation of key questions by a group of experts, literature searches and assessments were performed. Papers published up to 1 December 2020 and written in English were included in the literature review. PARTICIPANTS/MATERIALS SETTING METHODS Based on the collected evidence, recommendations were formulated and discussed within specialist subgroups and then presented to the core guideline development group (GDG) until consensus was reached. A stakeholder review was organized after finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help clinicians to apply best care for women with endometriosis. Although studies mostly focus on women of reproductive age, the guideline also addresses endometriosis in adolescents and postmenopausal women. The guideline outlines the diagnostic process for endometriosis, which challenges laparoscopy and histology as gold standard diagnostic tests. The options for treatment of endometriosis-associated pain symptoms include analgesics, medical treatments and surgery. Non-pharmacological treatments are also discussed. For management of endometriosis-associated infertility, surgical treatment and/or medically assisted reproduction are feasible. While most of the more recent studies confirm previous ESHRE recommendations, there are five topics in which significant changes to recommendations were required and changes in clinical practice are to be expected. LIMITATIONS REASONS FOR CAUTION The guideline describes different management options but, based on existing evidence, no firm recommendations could be formulated on the most appropriate treatments. Also, for specific clinical issues, such as asymptomatic endometriosis or extrapelvic endometriosis, the evidence is too scarce to make evidence-based recommendations. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in endometriosis care, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in endometriosis. STUDY FUNDING/COMPETING INTERESTS The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive payments. C.M.B. reports grants from Bayer Healthcare and the European Commission; Participation on a Data Safety Monitoring Board or Advisory Board with ObsEva (Data Safety Monitoring Group) and Myovant (Scientific Advisory Group). A.B. reports grants from FEMaLE executive board member and European Commission Horizon 2020 grant; consulting fees from Ethicon Endo Surgery, Medtronic; honoraria for lectures from Ethicon; and support for meeting attendance from Gedeon Richter; A.H. reports grants from MRC, NIHR, CSO, Roche Diagnostics, Astra Zeneca, Ferring; Consulting fees from Roche Diagnostics, Nordic Pharma, Chugai and Benevolent Al Bio Limited all paid to the institution; a pending patent on Serum endometriosis biomarker; he is also Chair of TSC for STOP-OHSS and CERM trials. O.H. reports consulting fees and speaker's fees from Gedeon Richter and Bayer AG; support for attending meetings from Gedeon-Richter, and leadership roles at the Finnish Society for Obstetrics and Gynecology and the Nordic federation of the societies of obstetrics and gynecology. L.K. reports consulting fees from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; honoraria for lectures from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; support for attending meetings from Gedeon Richter, AstraZeneca, Novartis, Dr KADE/Besins, Palleos Healthcare, Roche, Mithra; he also has a leadership role in the German Society of Gynecological Endocrinology (DGGEF). M.K. reports grants from French Foundation for Medical Research (FRM), Australian Ministry of Health, Medical Research Future Fund and French National Cancer Institute; support for meeting attendance from European Society for Gynaecological Endoscopy (ESGE), European Congress on Endometriosis (EEC) and ESHRE; She is an advisory Board Member, FEMaLe Project (Finding Endometriosis Using Machine Learning), Scientific Committee Chair for the French Foundation for Research on Endometriosis and Scientific Committee Chair for the ComPaRe-Endometriosis cohort. A.N. reports grants from Merck SA and Ferring; speaker fees from Merck SA and Ferring; support for meeting attendance from Merck SA; Participation on a Data Safety Monitoring Board or Advisory Board with Nordic Pharma and Merck SA; she also is a board member of medical advisory board, Endometriosis Society, the Netherlands (patients advocacy group) and an executive board member of the World Endometriosis Society. E.S. reports grants from National Institute for Health Research UK, Rosetrees Trust, Barts and the London Charity; Royalties from De Gruyter (book editor); consulting fees from Hologic; speakers fees from Hologic, Johnson & Johnson, Medtronic, Intuitive, Olympus and Karl Storz; Participation in the Medicines for Women's Health Expert Advisory Group with Medicines and Healthcare Products Regulatory Agency (MHRA); he is also Ambassador for the World Endometriosis Society. C.T. reports grants from Merck SA; Consulting fees from Gedeon Richter, Nordic Pharma and Merck SA; speaker fees from Merck SA, all paid to the institution; and support for meeting attendance from Ferring, Gedeon Richter and Merck SA. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose (Full disclaimer available at www.eshre.eu/guidelines.).
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Affiliation(s)
- Christian M Becker
- Nuffield Department of Women’s and Reproductive Health, Endometriosis CaRe
Centre, University of Oxford, Oxford, UK
| | - Attila Bokor
- Department of Obstetrics and Gynecology, Semmelweis University,
Budapest, Hungary
| | - Oskari Heikinheimo
- Department of Obstetrics & Gynecology, University of Helsinki and Helsinki
University Hospital, Helsinki, Finland
| | - Andrew Horne
- EXPPECT Centre for Endometriosis and Pelvic Pain, MRC Centre for Reproductive
Health, University of Edinburgh, Edinburgh, UK
| | - Femke Jansen
- EndoHome—Endometriosis Association Belgium, Belgium
| | - Ludwig Kiesel
- Department of Gynecology and Obstetrics, University Hospital
Muenster, Muenster, Germany
| | | | - Marina Kvaskoff
- Paris-Saclay University, UVSQ, Univ. Paris-Sud, Inserm, Gustave Roussy,
“Exposome and Heredity” Team, CESP, Villejuif, France
| | - Annemiek Nap
- Department of Gynaecology and Obstetrics, Radboudumc, Nijmegen,
The Netherlands
| | | | - Ertan Saridogan
- Department of Obstetrics and Gynaecology, University College London
Hospital, London, UK
- Elizabeth Garrett Anderson Institute for Women’s Health, University College
London, London, UK
| | - Carla Tomassetti
- Department of Obstetrics and Gynaecology, Leuven University Fertility Center,
University Hospitals Leuven, Leuven, Belgium
- Faculty of Medicine, Department of Development and Regeneration, LEERM (Lab of
Endometrium, Endometriosis and Reproductive Medicine), KU Leuven, Leuven,
Belgium
| | - Nehalennia van Hanegem
- Department of Reproductive Medicine and Gynecology, University Medical Center
Utrecht, Utrecht, The Netherlands
| | - Nicolas Vulliemoz
- Department of Woman Mother Child, Fertility Medicine and Gynaecological
Endocrinology, Lausanne University Hospital, Lausanne, Switzerland
| | - Nathalie Vermeulen
- European Society of Human Reproduction and Embryology,
Strombeek-Bever, Belgium
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Harzif AK, Pratama G, Maidarti M, Prameswari N, Shadrina A, Mutia K, Iffanolida PA, Wiweko B. Ovarian cortex freezing as a method of fertility preservation in endometriosis: A case report. Ann Med Surg (Lond) 2022; 74:103222. [PMID: 35145654 PMCID: PMC8818937 DOI: 10.1016/j.amsu.2021.103222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/25/2021] [Accepted: 12/26/2021] [Indexed: 11/17/2022] Open
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Li P, Bai Y, Shan B, Zhang W, Liu Z, Zhu Y, Xu X, Chen Q, Sheng X, Deng X, Guo Z, Zhang D, Wang H, Zhang Y, Hu Y. Exploration of Potential Diagnostic Value of Protein Content in Serum Small Extracellular Vesicles for Early-Stage Epithelial Ovarian Carcinoma. Front Oncol 2021; 11:707658. [PMID: 34604046 PMCID: PMC8479155 DOI: 10.3389/fonc.2021.707658] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 08/19/2021] [Indexed: 12/20/2022] Open
Abstract
Epithelial ovarian carcinoma (EOC) is one of the most common gynecologic malignancies with a high mortality rate. Serum biomarkers and imaging approaches are insufficient in identifying EOC patients at an early stage. This study is to set up a combination of proteins from serum small extracellular vesicles (sEVs) for the diagnosis of early-stage EOC and to determine its performance. A biomarker for early-stage ovarian cancer (BESOC) cohort was used as a Chinese multi-center population-based biomarker study and registered as a Chinese Clinical Trial ChiCTR2000040136. The sEV protein levels of CA125, HE4, and C5a were measured in 299 subjects. Logistic regression was exploited to calculate the odds ratio and to create the sEV protein model for the predicted probability and subsequently receiver-operating characteristic (ROC) analysis. The combined sEV marker panel of CA125, HE4, and C5a as a sEV model obtained an area under curve (AUC) of 0.912, which was greater than the serum model (0.809), by ROC analysis to identify EOC patients from the whole cohort. With the cutoff of 0.370, the sensitivity and specificity of the sEV model were 0.80 and 0.89, which were much better performance than the serum markers (sensitivity: 0.55~0.66; specificity: 0.59~0.68) and the risk of ovarian malignancy algorithm (ROMA) index approved by the U.S. Food and Drug Administration (sensitivity: 0.65; specificity: 0.61), to identify EOC patients from patients with benign ovarian diseases or other controls. The sEV levels of CA125 significantly differed among early-stage and late-stage EOC (p < 0.001). Moreover, the AUC of ROC to identify early-stage EOC patients was 0.888. Further investigation revealed that the sEV levels of these 3 proteins significantly decreased after cytoreductive surgery (CA125, p = 0.008; HE4, p = 0.025; C5a, p = 0.044). In summary, our study showed that CA125, HE4, and C5a levels in serum sEVs can identify EOC patients at the early stage, elucidating the possibility of using a sEV model for the diagnosis of early-stage EOC.
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Affiliation(s)
- Pu Li
- Department of Gynecology Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China
| | - Yuezong Bai
- 3D Medicines Inc., Shanghai, China.,Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Boer Shan
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Wei Zhang
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | | | - Yingjie Zhu
- Department of Gynecology, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | | | - Qian Chen
- Department of Gynecology, Yunnan Tumor Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Xiujie Sheng
- Key Laboratory for Major Obstetric Diseases of Guangdong Province, Gynecology Department of the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xiaoyang Deng
- Gynecology Department, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Zhengchen Guo
- Department of Gynecology Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China
| | | | - Huaying Wang
- Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | | | - Yuanjing Hu
- Department of Gynecology Oncology, Tianjin Central Hospital of Obstetrics and Gynecology, Tianjin, China
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Lee JK, Ahn SH, Kim HI, Lee YJ, Kim S, Han K, Kim MD, Seo SK. Therapeutic Efficacy of Catheter-directed Ethanol Sclerotherapy and Its Impact on Ovarian Reserve in Patients with Ovarian Endometrioma at Risk of Decreased Ovarian Reserve: A Preliminary Study. J Minim Invasive Gynecol 2021; 29:317-323. [PMID: 34469826 DOI: 10.1016/j.jmig.2021.08.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 08/24/2021] [Accepted: 08/25/2021] [Indexed: 10/20/2022]
Abstract
STUDY OBJECTIVE To investigate the therapeutic efficacy of catheter-directed ethanol sclerotherapy (CDS) and its effect on ovarian reserve in patients with endometrioma at risk of decreased ovarian reserve. DESIGN Retrospective study. SETTING Teaching hospital. PATIENTS We evaluated 18 patients with ovarian endometrioma measuring ≥3 cm and preprocedural serum antimüllerian hormone (AMH) levels of <2 ng/mL. INTERVENTIONS An 8.5-F catheter was inserted either transabdominally or transvaginally into the endometrioma. After aspiration, sclerotherapy with 99% ethanol was performed, with a subsequent 20-minute ethanol retention. MEASUREMENTS AND MAIN RESULTS Ultrasonography was performed preprocedurally and 6 months after CDS to evaluate any recurrence or changes in cyst size. Furthermore, serum AMH levels, cancer antigen 125 (CA-125) levels, and the visual analog scale scores for dysmenorrhea were obtained to analyze the ovarian reserve and treatment efficacy, preprocedurally and at 6 months after CDS. The mean cyst size on ultrasonography and serum CA-125 levels decreased 6 months after CDS (p <.001 and p = .001, respectively). All patients reported a decreased visual analog scale score for dysmenorrhea (p <.001). However, the difference in serum AMH levels before and after CDS was statistically insignificant (p = .875). CONCLUSION CDS was efficacious in reducing pain and serum CA-125 levels in patients with low AMH levels without adversely affecting their ovarian reserve.
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Affiliation(s)
- Jae Kyung Lee
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea
| | - So Hyun Ahn
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea
| | - Hye In Kim
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea
| | - Yong Jae Lee
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea
| | - Sunghoon Kim
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea
| | | | | | - Seok Kyo Seo
- Departments of Obstetrics and Gynecology (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo); Severance Hospital, and Institute of Women's Life Medical Science, (Drs. J.K. Lee, Ahn, H.I. Kim, Y.J. Lee, S. Kim, and Seo), Yonsei University College of Medicine, Seoul, Korea.
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Kimber-Trojnar Ż, Pilszyk A, Niebrzydowska M, Pilszyk Z, Ruszała M, Leszczyńska-Gorzelak B. The Potential of Non-Invasive Biomarkers for Early Diagnosis of Asymptomatic Patients with Endometriosis. J Clin Med 2021; 10:2762. [PMID: 34201813 PMCID: PMC8268879 DOI: 10.3390/jcm10132762] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2021] [Revised: 06/13/2021] [Accepted: 06/17/2021] [Indexed: 02/07/2023] Open
Abstract
Endometriosis is a disease that affects women of reproductive age and has a significantly negative impact on their well-being. The main symptoms are dysmenorrhoea, chronic pelvic pain and infertility. In many patients the diagnostic process is very long and can take up to 8-12 years. Laparoscopy, an invasive method, is still necessary to confirm the diagnosis. Therefore, development of more effective diagnostic markers appears to be of the utmost importance for early diagnosis of endometriosis and provision of appropriate treatment. From a clinical point of view, detection of early-stage endometriosis in asymptomatic patients is an ideal situation since early diagnosis of endometriosis may delay the onset of symptoms as well as prevent progression and complications. In the meantime, Cancer Antigen 125 (CA-125) is still the most frequently studied and used marker. Other glycoproteins, growth factors and immune markers seem to play an important role. However, the search for an ideal endometriosis marker is still underway. Further studies into the pathogenesis of endometriosis will help to identify biomarkers or sets of biomarkers with the potential to improve and speed up the diagnostic process in a non-invasive way.
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Affiliation(s)
- Żaneta Kimber-Trojnar
- Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland; (A.P.); (M.N.); (M.R.); (B.L.-G.)
| | - Aleksandra Pilszyk
- Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland; (A.P.); (M.N.); (M.R.); (B.L.-G.)
| | - Magdalena Niebrzydowska
- Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland; (A.P.); (M.N.); (M.R.); (B.L.-G.)
| | - Zuzanna Pilszyk
- Scientific Association at the 2nd Clinic of Gynecology and Obstetrics, Wroclaw Medical University, 50-367 Wrocław, Poland;
| | - Monika Ruszała
- Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland; (A.P.); (M.N.); (M.R.); (B.L.-G.)
| | - Bożena Leszczyńska-Gorzelak
- Department of Obstetrics and Perinatology, Medical University of Lublin, 20-090 Lublin, Poland; (A.P.); (M.N.); (M.R.); (B.L.-G.)
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Abstract
A clinically reliable non-invasive test for endometriosis is expected to reduce the diagnostic delay. Although varieties of biomarkers have been investigated for decades, and cancer antigen-125, cancer antigen-199, interleukin-6, and urocortin were the most studied ones among hundreds of biomarkers, no clinically reliable biomarkers have been confirmed so far. Some emerging technologies including “omics” technologies, molecular imaging techniques, and microRNAs are promising in solving these challenges, but their utility to detect endometriosis has yet to be verified. New combinations of researched indicators or other non-invasive methods and further exploration of the emerging technologies may be new targets and future research hotspots for non-invasive diagnosis of endometriosis. In conclusion, researches of biomarkers for the detection of endometriosis are still ongoing and may benefit from novel molecular biology, bioinformatics methods and a combination of more diverse monitoring methods. Though it will be a daunting task, the identification of a specific set of diagnostic biomarkers will undoubtedly improve the status of endometriosis.
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34
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Greenbaum H, Galper BEL, Decter DH, Eisenberg VH. Endometriosis and autoimmunity: Can autoantibodies be used as a non-invasive early diagnostic tool? Autoimmun Rev 2021; 20:102795. [DOI: 10.1016/j.autrev.2021.102795] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 01/08/2021] [Indexed: 12/21/2022]
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Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet 2021; 397:839-852. [PMID: 33640070 DOI: 10.1016/s0140-6736(21)00389-5] [Citation(s) in RCA: 550] [Impact Index Per Article: 137.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Revised: 08/09/2020] [Accepted: 08/14/2020] [Indexed: 12/14/2022]
Abstract
Endometriosis is a common disease affecting 5-10% of women of reproductive age globally. However, despite its prevalence, diagnosis is typically delayed by years, misdiagnosis is common, and delivery of effective therapy is prolonged. Identification and prompt treatment of endometriosis are essential and facilitated by accurate clinical diagnosis. Endometriosis is classically defined as a chronic, gynaecological disease characterised by endometrial-like tissue present outside of the uterus and is thought to arise by retrograde menstruation. However, this description is outdated and no longer reflects the true scope and manifestations of the disease. The clinical presentation is varied, the presence of pelvic lesions is heterogeneous, and the manifestations of the disease outside of the female reproductive tract remain poorly understood. Endometriosis is now considered a systemic disease rather than a disease predominantly affecting the pelvis. Endometriosis affects metabolism in liver and adipose tissue, leads to systemic inflammation, and alters gene expression in the brain that causes pain sensitisation and mood disorders. The full effect of the disease is not fully recognised and goes far beyond the pelvis. Recognition of the full scope of the disease will facilitate clinical diagnosis and allow for more comprehensive treatment than currently available. Progestins and low-dose oral contraceptives are unsuccessful in a third of symptomatic women globally, probably as a result of progesterone resistance. Oral gonadotropin-releasing hormone (GnRH) antagonists constitute an effective and tolerable therapeutic alternative when first-line medications do not work. The development of GnRH antagonists has resulted in oral drugs that have fewer side-effects than other therapies and has allowed for rapid movement between treatments to optimise and personalise endometriosis care. In this Review, we discuss the latest understanding of endometriosis as a systemic disease with multiple manifestations outside the parameters of classic gynaecological disease.
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Affiliation(s)
- Hugh S Taylor
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
| | - Alexander M Kotlyar
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
| | - Valerie A Flores
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA
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36
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Misir S, Hepokur C, Oksasoglu B, Yildiz C, Yanik A, Aliyazicioglu Y. Circulating serum miR-200c and miR-34a-5p as diagnostic biomarkers for endometriosis. J Gynecol Obstet Hum Reprod 2021; 50:102092. [PMID: 33601073 DOI: 10.1016/j.jogoh.2021.102092] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/28/2021] [Accepted: 02/03/2021] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Endometriosis is defined by the presence of endometrial glands and stroma grow in areas outside the uterus. A simple blood test for endometriosis-specific biomarkers would offer a more timely accurate diagnosis of the disease and could lead to earlier treatment intervention. Alterations in microRNA (miRNA) levels in blood may reflect changes during normal physiologic processes and have been related to several pathologic conditions, including gynecologic diseases. In the present study, we aim to evaluate the level of serum miR-34a-5p and miR-200c from women with and without endometriosis, and to explore the potential of miRNAs as reliable non-invasive biomarkers in the diagnosis of endometriosis. METHODS Expression levels of miRNAs were performed by quantitative real-time polymerase chain reaction (qRT-PCR). Serum cancer antigen 125 (CA-125) levels were analyzed by autoanalyzer. RESULTS miR-34a-5p expression levels were decreased and miR-200c expression levels were increased in the endometriosis patients compared to the control group. According to the areas under the ROC curve (AUC) values, miR-200c and miR-34a-5p may serve as biomarkers for the diagnosis of endometriosis. Serum miR-34a-5p and miR-200c had a sensitivity of 78.95 % and 100 % and a specificity of 49.12 % and 100 %, respectively, for the detection of endometriosis. CONCLUSION Serum miRNAs may provide a promising opportunity for diagnosis of endometriosis. Understanding the role of circulating miRNAs will serve a better comprehension of the systemic effects of endometriosis and offer options for new treatments. It is clear that more work is needed in this area.
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Affiliation(s)
- Sema Misir
- Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkiye.
| | - Ceylan Hepokur
- Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58140 Sivas, Turkiye
| | - Bugra Oksasoglu
- Sarkisla Public Hospital, Clinic Of Obstetrics and Gynecology, 58140 Sivas, Turkiye
| | - Caglar Yildiz
- Department of Gynecology and Obstetrics, Medical Faculty of Sivas Cumhuriyet University, 58140 Sivas, Turkiye
| | - Ali Yanik
- Department of Gynecology and Obstetrics, Medical Faculty of Sivas Cumhuriyet University, 58140 Sivas, Turkiye
| | - Yüksel Aliyazicioglu
- Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkiye
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Tang T, Lai H, Huang X, Gu L, Shi H. Application of serum markers in diagnosis and staging of ovarian endometriosis. J Obstet Gynaecol Res 2021; 47:1441-1450. [PMID: 33448139 DOI: 10.1111/jog.14654] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 12/01/2020] [Accepted: 12/26/2020] [Indexed: 12/21/2022]
Abstract
AIMS Laparoscopic surgery is widely used for diagnosing ovarian endometriosis but it has medical risks. This study explored the application of blood indicators in diagnosis and staging of ovarian endometriosis, aiming to develop a noninvasive diagnostic method. METHODS A total of 190 ovarian endometriosis patients were included in observation group, among these participants, 77 patients among them were stages I-II, and the rest 113 patients were stages III-IV, and a total of 103 healthy women as control group. Serum biochemical indexes, tumor markers, and cytokines levels in two groups were used for the diagnosis and staging of the disease. Area under the receiver operating characteristic (ROC) curve (AUC) predicted the value of individual and joint tests for indicators. RESULTS Biochemical indexes, namely, alkaline phosphatase (ALP), total protein (TP), and glucose (Glu) could distinguish patients from normal women; and that ALP and Glu could indicate disease staging. In tumor markers, alpha fetoprotein (AFP), carcinoembryonic antigen (CA) 125, CA199 and human epididymis protein 4 (HE4) helped to diagnose endometriosis; CA125, HE4, and cytokeratin 19 fragment (CYFRA21-1) could differentiate stages. In cytokines, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, interleukin (IL)-6, soluble fms-like tyrosine kinase receptor 1 (sflt-1), monocyte chemoattractant protein (MCP)-1 therefore, have values to diagnose endometriosis; VEGF, TNF-α, IL-6, and sflt-1 helped to differentiate disease staging. CONCLUSION Serological indicators in ovarian endometriosis patients were different from healthy women, which were of certain differential values in diagnosis and disease staging. The current study provided a novel strategy for endometriosis diagnosis.
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Affiliation(s)
- Ting Tang
- Department of Gynaecology, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, China
| | - Huichao Lai
- Department of Gynaecology, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, China
| | - Xuemei Huang
- Department of Gynaecology, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, China
| | - Liqin Gu
- Department of Gynaecology, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, China
| | - Haiying Shi
- Department of Assisted Reproduction, Ganzhou People's Hospital of Jiangxi Province, Ganzhou, China
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Zafari N, Tarafdari AM, Izadi P, Noruzinia M, Yekaninejad MS, Bahramy A, Mohebalian A. A Panel of Plasma miRNAs 199b-3p, 224-5p and Let-7d-3p as Non-Invasive Diagnostic Biomarkers for Endometriosis. Reprod Sci 2021; 28:991-999. [PMID: 33398851 DOI: 10.1007/s43032-020-00415-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 11/25/2020] [Indexed: 11/29/2022]
Abstract
The objective of this study was to investigate whether the combination of miR-224-5p, miR-199-3p, and let-7d-3p is a suitable diagnostic panel for endometriosis. Twenty-five women with endometriosis (case) and twenty-five women without any sign of endometriosis (controls) were included. Peripheral blood specimens were collected from all these women who were a proper candidate for laparoscopy before surgery. Total RNA was isolated to synthesize complementary DNA. Expression of miR-199b-3p, miR-224-5p, and let-7d-3p was analyzed by RT-qPCR. To estimate the performance of the identified miRNAs for endometriosis diagnosis, we performed ROC curves analysis. There was an upregulation of miRNAs 199b-3p (P value < 0.001) and down-regulation of 224-5p (P value < 0.001) and miRNA let-7d-3p (P value < 0.05) in women with endometriosis compared to non-endometriosis women. The diagnostic accuracy of miRNAs 199b-3p, 224-5p, and let-7d-3p was measured by AUC which was 0.843 (sensitivity = 96% and specificity = 80%), 0.914 (sensitivity = 84% and specificity = 80%), and 0.696 (sensitivity = 80% and specificity = 56%) for miRNAs 199b-3p, 224-5p, and let-7d-3p, respectively. In combination, they showed the highest accuracy with the AUC 0.992 (sensitivity = 96% and specificity = 100%). In conclusion(s) the levels of miRNAs 199b-3p, 224-5p, and Let-7d-3p in plasma are potential diagnostic biomarkers for endometriosis patients.
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Affiliation(s)
- Narges Zafari
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Azam Manshadi Tarafdari
- Department of Gynecology and Obstetrics, Tehran University of Medical Sciences, Tehran, Iran
| | - Pantea Izadi
- Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mehrdad Noruzinia
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mir Saead Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Afshin Bahramy
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Mohebalian
- Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Guralp O, Kaya B, Tüten N, Kucur M, Malik E, Tüten A. Non-invasive diagnosis of endometriosis and moderate-severe endometriosis with serum CA125, endocan, YKL-40, and copeptin quadruple panel. J OBSTET GYNAECOL 2020; 41:927-932. [PMID: 33064040 DOI: 10.1080/01443615.2020.1803245] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate - severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal - mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate - severe endometriosis group compared to the mild -moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate - severe endometriosis. Further studies are needed to prove the efficacy of this panel.Impact statementWhat is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis.What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis.What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.
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Affiliation(s)
- Onur Guralp
- University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Carl von Ossietzky Oldenburg University, Oldenburg, Germany
| | - Baris Kaya
- Department of Obstetrics and Gynecology, Kosuyolu Hospital, Yeditepe University, Istanbul, Turkey
| | - Nevin Tüten
- Department of Obstetrics and Gynecology, Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
| | - Mine Kucur
- Department of Biochemistry, Istanbul Cerrahpasa University, Istanbul, Turkey
| | - Eduard Malik
- University Hospital for Gynecology and Obstetrics, Klinikum Oldenburg AöR, Carl von Ossietzky Oldenburg University, Oldenburg, Germany
| | - Abdullah Tüten
- Department of Obstetrics and Gynecology, Istanbul Cerrahpasa University, Istanbul, Turkey
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Toll-Like Receptor 2 Expression as a New Hallmark of Advanced Endometriosis. Cells 2020; 9:cells9081813. [PMID: 32751735 PMCID: PMC7464841 DOI: 10.3390/cells9081813] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/24/2020] [Accepted: 07/27/2020] [Indexed: 12/27/2022] Open
Abstract
Recent evidence suggests that immunological aspects play a pivotal role in this disorder. Toll-like receptor 2 (TLR2) is crucial in recognizing microbial infections and mediating innate immune response. The objective of our study was to rate with flow cytometry the levels of several subsets of dendritic cells, monocytes, and basic peripheral blood lymphocytes expressing TLR2, aiming at the determination of a possible correlation between the expression of TLR2 and the clinical outcomes of endometriosis in 40 patients and 40 age-matched healthy women. Our study showed the importance of TLR2 expression, mainly on myeloid dendritic cells (mDCs) and B cells in patients with endometriosis. Both mDCs BDCA1+CD19-TLR2+ and B lymphocytes CD19+TLR-2+ proved useful in the differentiation of affected individuals with stages 3–4 of the disease (area under the receiver operating characteristic curve /AUC/ = 0.96, p < 0.0001 for mDCs; AUC = 0.78, p = 0.0001 for B lymphocytes), and those presenting adhesion (AUC = 0.92, p < 0.0001 for mDCs; AUC = 0.82, p < 0.0001 for B lymphocytes) or infertility (AUC = 0.83, p < 0.0001 for mDCs; AUC = 0.73, p = 0.006 for B lymphocytes). Our findings suggest that the levels of TLR2-expressing cells, particularly mDCs and B lymphocytes, may be an effective biomarker of endometriosis, because the disease currently lacks clinically useful noninvasive biomarkers enabling early and cost-effective diagnosis.
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Méar L, Pineau C, Vialard F, Velez de la Calle JF. Endometriosis screening in patients attending an IVF clinic: a proof-of-concept retrospective cohort study. HUM FERTIL 2020; 25:313-322. [PMID: 32684058 DOI: 10.1080/14647273.2020.1795731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Given that (i) endometriosis affects approximately 40% of women diagnosed with fertility problems and (ii) this condition may be an underestimated cause of idiopathic infertility, it is essential to identify high-risk patients for laparoscopic screening and reduce the diagnostic delay. We performed a retrospective analysis of 312 women (208 diagnosed with endometriosis and 104 controls) admitted to an in vitro fertilisation (IVF) unit in the city of Brest (France) between June 2007 and July 2014. As part of the women's infertility treatment, levels of cancer antigen 125 (CA-125) were assayed in blood samples collected on the day of oocyte retrieval. Surplus serum was used to set up a new sperm agglutination test. It was observed that sperm agglutination was significantly correlated with endometriosis and CA-125 levels (p < 0.01 for both). By building a decision tree, we identified a subpopulation of patients with low CA-125 levels and a high risk of endometriosis. This proof-of-concept study constitutes a first step towards a high-quality, controlled, multi-centre trial. If our preliminary results are confirmed, the decision tree should improve the medical care given to women in IVF programmes by identifying potential endometriosis sufferers for laparoscopic examination and enabling them to be counselled about precautionary measures.
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Affiliation(s)
- Loren Méar
- Univ Rennes, INSERM, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes Cedex, France.,GIG-EA7404, Université de Versailles Saint-Quentin-en-Yvelines - Paris Saclay, UFR Sciences de la Santé-Simone Veil, Montigny-le Bretonneux, France.,Protim, Univ Rennes, Rennes Cedex, France
| | - Charles Pineau
- Univ Rennes, INSERM, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, Rennes Cedex, France.,Protim, Univ Rennes, Rennes Cedex, France
| | - François Vialard
- GIG-EA7404, Université de Versailles Saint-Quentin-en-Yvelines - Paris Saclay, UFR Sciences de la Santé-Simone Veil, Montigny-le Bretonneux, France.,Department of Biology of Reproduction, Cytogenetics and Genetics, Centre Hospitalier de Poissy-Saint Germain, CS 73082, Poissy, France
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The reduction of CA 125 serum levels in BRCA 1/2 mutation carriers after risk-reducing salpingo-oophorectomy is only partially associated with surgery: a prospective cohort, other biomarker controlled, study. Eur J Cancer Prev 2020; 29:350-356. [DOI: 10.1097/cej.0000000000000606] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Biomarkers for the Noninvasive Diagnosis of Endometriosis: State of the Art and Future Perspectives. Int J Mol Sci 2020; 21:ijms21051750. [PMID: 32143439 PMCID: PMC7084761 DOI: 10.3390/ijms21051750] [Citation(s) in RCA: 93] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2019] [Revised: 02/27/2020] [Accepted: 03/02/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Early and accurate diagnosis of endometriosis is crucial for the management of this benign, yet debilitating pathology. Despite the advances of modern medicine, there is no common ground regarding the pathophysiology of this disease as it continues to affect the quality of life of millions of women of reproductive age. The lack of specific symptoms often determines a belated diagnosis. The gold standard remains invasive, surgery followed by a histopathological exam. A biomarker or a panel of biomarkers is easy to measure, usually noninvasive, and could benefit the clinician in both diagnosing and monitoring the treatment response. Several studies have advanced the idea of biomarkers for endometriosis, thereby circumventing unnecessary invasive techniques. Our paper aims at harmonizing the results of these studies in the search of promising perspectives on early diagnosis. METHODS We selected the papers from Google Academic, PubMed, and CrossRef and reviewed recent articles from the literature, aiming to evaluate the effectiveness of various putative serum and urinary biomarkers for endometriosis. RESULTS The majority of studies focused on a panel of biomarkers, rather than a single biomarker and were unable to identify a single biomolecule or a panel of biomarkers with sufficient specificity and sensitivity in endometriosis. CONCLUSION Noninvasive biomarkers, proteomics, genomics, and miRNA microarray may aid the diagnosis, but further research on larger datasets along with a better understanding of the pathophysiologic mechanisms are needed.
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Govorov I, Sitkin S, Pervunina T, Moskvin A, Baranenko D, Komlichenko E. Metabolomic Biomarkers in Gynecology: A Treasure Path or a False Path? Curr Med Chem 2020; 27:3611-3622. [PMID: 30608036 DOI: 10.2174/0929867326666190104124245] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 12/21/2018] [Accepted: 12/31/2018] [Indexed: 12/27/2022]
Abstract
Omic-technologies (genomics, transcriptomics, proteomics and metabolomics) have become more important in current medical science. Among them, it is metabolomics that most accurately reflects the minor changes in body functioning, as it focuses on metabolome - the group of the metabolism products, both intermediate and end. Therefore, metabolomics is actively engaged in fundamental and clinical studies and search for potential biomarkers. The biomarker could be used in diagnostics, management and stratification of the patients, as well as in prognosing the outcomes. The good example is gynecology, since many gynecological diseases lack effective biomarkers. In the current review, we aimed to summarize the results of the studies, devoted to the search of potential metabolomic biomarkers for the most common gynecological diseases.
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Affiliation(s)
- Igor Govorov
- Institute of Perinatology and Pediatric, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russian Federation
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
| | - Stanislav Sitkin
- Institute of Perinatology and Pediatric, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russian Federation
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
- North-Western State Medical University named after I.I. Mechnikov, St. Petersburg 191015, Russian Federation
| | - Tatyana Pervunina
- Institute of Perinatology and Pediatric, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russian Federation
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
| | - Alexey Moskvin
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
| | - Denis Baranenko
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
| | - Eduard Komlichenko
- Institute of Perinatology and Pediatric, Almazov National Medical Research Centre, Saint-Petersburg 197341, Russian Federation
- International Research Centre "Biotechnologies of the Third Millennium", ITMO University, Saint-Petersburg 197341, Russian Federation
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45
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Ilhan M, Gürağaç Dereli FT, Akkol EK. Novel Drug Targets with Traditional Herbal Medicines for Overcoming Endometriosis. Curr Drug Deliv 2019; 16:386-399. [PMID: 30588884 PMCID: PMC6637095 DOI: 10.2174/1567201816666181227112421] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 01/09/2023]
Abstract
Endometriosis is a disease in which the lining of the endometrium is found outside of the uterus. Recent medical treatments for endometriosis have adverse effects, limiting their long-term use. Furthermore, the recurrence of the disease after the cessation of therapy is quite common, and most patients need to continue treatment to maintain a hypoestrogenic environment till conception. Notwithstanding recent advances in computational and chemical practices, traditional medicines are considered the most consistent sources for the discovery of new drugs. Numerous medicinal plants and plantderived compounds have been tested against gynecological disorders, mainly endometriosis. This review aimed to describe the pharmacological activity profile of the medicinal plants and their active ingredients and draw attention to the discovery of multitargeted drug molecules for rational therapy.
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Affiliation(s)
- Mert Ilhan
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler 06330, Ankara, Turkey.,Department of Pharmacognosy, Faculty of Pharmacy, Van Yuzuncu Yil University, Tusba 65080, Van, Turkey
| | | | - Esra Küpeli Akkol
- Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler 06330, Ankara, Turkey
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Creed JM, Maggrah A, Usher R, Desa E, Harbottle A. How can mitochondrial DNA deletions act as a biomarker for the detection of endometriosis within the clinic? Biomark Med 2019; 14:5-8. [PMID: 31686548 DOI: 10.2217/bmm-2019-0435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Affiliation(s)
- Jennifer M Creed
- MDNA Life Sciences Inc., 2054 Vista Parkway, Ste 400, West Palm Beach, FL 33411, USA
| | - Andrea Maggrah
- MDNA Life Sciences Inc., 2054 Vista Parkway, Ste 400, West Palm Beach, FL 33411, USA
| | - Robert Usher
- MDNA Life Sciences Inc., 2054 Vista Parkway, Ste 400, West Palm Beach, FL 33411, USA
| | - Elise Desa
- MDNA Life Sciences Inc., 2054 Vista Parkway, Ste 400, West Palm Beach, FL 33411, USA
| | - Andrew Harbottle
- MDNA Life Sciences Inc., 2054 Vista Parkway, Ste 400, West Palm Beach, FL 33411, USA
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47
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Lee Y, Lee Y, Lee S, Jung S, Chon S. Correlation of preoperative biomarkers with severity of adhesion in endometriosis. J Gynecol Obstet Hum Reprod 2019; 49:101637. [PMID: 31520750 DOI: 10.1016/j.jogoh.2019.101637] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 07/26/2019] [Accepted: 09/10/2019] [Indexed: 01/04/2023]
Abstract
This study was undertaken to evaluate the correlation between preoperative Serum markers and pelvic adhesions in endometriosis patients and to explore the markers' clinical value for outcome prediction. Preoperative blood Serum and CA 125 results were obtained and pelvic adhesion scores were calculated. The patient group with adhesion scores less than 28 points was defined as the mild adhesion group, and those with a score of 28 or more were members of the severe adhesion group. The CA 125 level was significantly higher in the severe adhesion group than in the mild adhesion group. The CA 125 level, size of the largest cyst, and WBC count were associated with the level of pelvic adhesion. Adhesion scores were significantly higher in the CA 125 ≥ 35 U/mL group than in the CA 125 < 35 U/mL group. Patients with a preoperative CA 125 level higher than 35 U/mL are at high risk for pelvic adhesion.
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Affiliation(s)
- Yoojung Lee
- Department of Obstetrics and Gynecology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Yaeheun Lee
- Department of Obstetrics and Gynecology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Seungho Lee
- Department of Obstetrics and Gynecology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
| | - Sunyong Jung
- Department of Obstetrics and Gynecology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Seungjoo Chon
- Department of Obstetrics and Gynecology, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea
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Braga DPAF, Montani DA, Setti AS, Turco EGL, Oliveira-Silva D, Borges E. Metabolomic profile as a noninvasive adjunct tool for the diagnosis of Grades III and IV endometriosis-related infertility. Mol Reprod Dev 2019; 86:1044-1052. [PMID: 31215101 DOI: 10.1002/mrd.23221] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 04/18/2019] [Accepted: 05/16/2019] [Indexed: 01/09/2023]
Abstract
The aim of the present case-control study was to develop a noninvasive adjuvant tool for the diagnosis of endometriosis. Serum samples from 100 patients undergoing intracytoplasmic sperm injection were split into two groups according to the cause of infertility: an endometriosis group (n = 50), consisting of samples derived from patients with Grade III and IV endometriosis, and a control group (n = 50), comprising samples derived from patients with isolated male factor infertility. The metabolomic profile of each sample was obtained, through mass spectrometry. Partial least squares discriminant analysis was able to clearly classify the endometriosis and control groups. Ten potential biomarkers were selected based on their importance for model prediction. These ions were used to build the receiver-operating characteristic curve, which presented an area under the curve of 0.904 (95% confidence interval: 0.796-0.985). To validate the model, 30 other samples from infertile women without any evidence of endometriosis were tested. Considering these ions as possible biomarkers, the model was able to correctly classify 84% of the patients. Finally, a similar prediction potential was observed in the model validated set, when samples from the disease-free group were tested. Serum metabolomics may be useful as a noninvasive adjunct tool for the selection of patients who must undergo laparoscopy for definitive endometriosis diagnosis.
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Affiliation(s)
- Daniela P A F Braga
- Departamento de Pesquisa Científica, Fertility Medical Group, São Paulo, Brazil
| | - Daniela A Montani
- Departamento de Química Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo-UNIFESP, Diadema, Brazil
| | - Amanda S Setti
- Departamento de Pesquisa Científica, Fertility Medical Group, São Paulo, Brazil
| | - Edson G Lo Turco
- Departamento de Cirurgia, Disciplina de Urologia, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil
| | - Diogo Oliveira-Silva
- Departamento de Química Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo-UNIFESP, Diadema, Brazil
| | - Edson Borges
- Departamento de Química Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo-UNIFESP, Diadema, Brazil
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Endometriosis-Associated Ovarian Cancer: Population Characteristics and Prognosis. Int J Gynecol Cancer 2019; 28:1251-1257. [PMID: 30142123 DOI: 10.1097/igc.0000000000001317] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
OBJECTIVE The aim of this study was to analyze and compare the clinicopathologic features and prognosis of clear cell ovarian carcinoma (CCOC) and endometrioid ovarian carcinoma (EOC) associated or not with endometriosis. METHODS This was a reconstituted cohort study from a single-institution Brazilian cancer center approved under review board no. 68150617.7.0000.5404 with 50 patients with CCOC and EOC diagnosed between 1995 and 2016, followed up until 2017. Clinicopathologic characteristics and survival outcomes were analyzed. RESULT(S) There were 23 women (46%) with CCOC and 27 with EOC (54%); 80% of those women had histologic confirmation of endometriosis; 42% were nulliparous, and 42% were premenopausal; and cancer antigen 125 was elevated in both International Federation of Gynecology and Obstetrics stages I-II disease (mean, 614.7 Ui/mL; range, 3-6030 Ui/mL) or International Federation of Gynecology and Obstetrics stages III-IV disease (mean, 2361.2 Ui/mL; range, 8-12771 Ui/mL). Women with EOC were 7 years younger than those with CCOC. When associated with endometriosis, CCOCs were more likely diagnosed at earlier stages. Endometrioid ovarian carcinoma and CCOC at initial stage and EOC at advanced stage share similar good prognosis. Univariate analysis showed that CCOC not associated with endometriosis has worse overall survival (OS). However, multivariate analysis showed that only abnormally elevated levels of cancer antigen 125 and advanced stage at diagnosis were significantly associated with reduced progression-free survival. Tumor stage remains the only prognostic factor for OS. CONCLUSIONS The presence of coexisting endometriosis did not change the prognosis of EOC but was associated with better OS in patients with CCOC. Patients with CCOC and EOC at initial stages and EOC at advanced stages have a good prognosis; however, CCOC at advanced stages had a sooner recurrence and shorter OS.
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50
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Choi YS, Kim S, Oh YS, Cho S, Hoon Kim S. Elevated serum interleukin-32 levels in patients with endometriosis: A cross-sectional study. Am J Reprod Immunol 2019; 82:e13149. [PMID: 31099938 DOI: 10.1111/aji.13149] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 04/06/2019] [Accepted: 05/13/2019] [Indexed: 12/21/2022] Open
Abstract
PROBLEM Recently, interleukin (IL)-32 has been suggested to be involved in the pathogenesis of endometriosis. The aim of this study was to investigate whether serum IL-32 level might be used as a biomarker for diagnosis of endometriosis. METHOD OF STUDY We recruited the serum samples of 50 patients with histologically confirmed endometriosis and 35 controls. Enzyme-linked immunosorbent assay was used to analyze the serum IL-32, IL-6, IL-10, tumour necrosis factor (TNF)-α, IL-1β, and CA-125 levels in patients with and without the disease and the diagnostic potentials of the cytokines were assessed using receiver operating characteristic curve and the area under the curve (AUC). RESULTS Among evaluated cytokines, only serum IL-32 levels showed significant differences between patients with and without endometriosis (1111.24 ± 149.59 vs 631.10 ± 120.23 ng/mL, P = 0.018, respectively). When the diagnostic power of serum IL-32 was evaluated, the AUC was 0.638 (95% confidence interval (CI): 0.521-0.766, P = 0.031). When serum IL-32 levels were combined with serum CA-125 levels, the AUC was increased to 0.749 (95% CI: 0.640-0.858, P < 0.001) with sensitivity and specificity of 60.0% and 82.9% at cutoff value of 0.640, which led to detect 25 more cases of endometriosis than the use of serum CA 125 with the cutoff value of 35 IU/mL (36/50 vs 11/50, P < 0.001) without sacrificing the specificity of the marker. CONCLUSION Serum IL-32 levels are elevated in patients with endometriosis, and with combination of serum CA-125 levels, it may serve as a potential biomarker for endometriosis.
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Affiliation(s)
- Young Sik Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Sinae Kim
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sang Oh
- Department of Obstetrics & Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - SiHyun Cho
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea.,Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sung Hoon Kim
- Department of Obstetrics & Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
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