The role of tumor necrosis factor alpha in regulating CYFRA 21-1 as a potential biomarker for endometriosis: A cross-sectional study

Nicko Pisceski Kusika Saputra, Saputra NPK, Samsulhadi Samsulhadi, Samsulhadi S, Hendarto H, Hendy Hendarto, Ashon Sa’adi, Ashon Saádi, Saádi A, Pudjirahardjo WJ, Widodo J Pudjirahardjo, Widodo Jatim Pudjirahardjo, I Wayan Arsana, Arsana IW, Yanuari R, Relly Yanuari, Relly Yanuari Primariawan, Sri Ratna Dwiningsih, Dwiningsih SR, Suri Dwi Lesmana, Lesmana SD
International journal of reproductive biomedicine · 2026 · vol. 24(5) , pp. 445–456 · doi:10.18502/ijrm.v24i5.21293 · PMID:42516819 · PMC13402962 · W7168277684
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This study found that higher intraperitoneal TNF-α levels in women with endometriosis correlated positively with CYFRA 21-1 levels, especially during the proliferative phase.

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This cross-sectional study investigated the relationship between tumor necrosis factor alpha (TNF-alpha) levels and CYFRA 21-1 concentrations in patients diagnosed with endometriosis. The researchers analyzed serum samples to determine if TNF-alpha regulates CYFRA 21-1 expression, evaluating its potential utility as a diagnostic biomarker for the disease. Results indicated a significant association between elevated TNF-alpha levels and increased CYFRA 21-1, supporting its role as a potential indicator of endometriotic activity. This paper is centrally about endometriosis — specifically examining inflammatory markers and their correlation with a proposed serum biomarker for diagnosis.

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Abstract

Background: Endometriosis is one of the most common gynecological conditions, and the gold standard for its diagnosis is laparoscopy. Cytokeratin fragment 21-1 (CYFRA 21-1) has emerged as a potential biomarker candidate due to its strong association with endometriosis. The mechanisms underlying the cleavage of cytokeratin-19 into CYFRA 21-1 remain unclear. Tumor necrosis factor alpha (TNF-α) may play a regulatory role in this process. Objective: This study aimed to analyze the correlation between intraperitoneal TNF-α levels and CYFRA 21-1 expression levels in women with endometriosis. Materials and Methods: This was an analytical study with a cross-sectional study design, involving 38 women diagnosed with endometriosis and 35 non-endometriosis women as controls. Both CYFRA 21-1 and TNF-α concentrations were measured using the Enzyme-Linked Immunosorbent Assay method. Urine creatinine was measured using the Electrochemiluminescence Immunoassay method, while clinical data were collected through medical records. Results: The mean intraperitoneal TNF-α level was significantly higher in the endometriosis group compared to controls (p < 0.001). A significant positive correlation was found between intraperitoneal TNF-α concentrations and CYFRA 21-1 levels (p < 0.001; r 0,662 [95% CI: 0.426-0.814]), indicating a strong association. Furthermore, a strong positive correlation was observed between the urinary CYFRA 21-1 to creatinine ratio and intraperitoneal TNF-α levels, particularly during the proliferative phase of the menstrual cycle. Conclusion: These findings suggest that TNF-α may influence CYFRA 21-1 expression in a cycle phase-dependent manner, supporting the potential role of CYFRA 21-1 as a non-invasive biomarker for endometriosis, particularly during the proliferative phase.
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Publication International Journal of Reproductive BioMedicine (IJRM) Record type Journal article Published 14 July 2026 Authors Nicko Pisceski Kusika Saputra | Samsulhadi Samsulhadi | Hendy Hendarto | Ashon Saádi | Widodo J Pudjirahardjo | I Wayan Arsana | Relly Yanuari | Sri Ratna Dwiningsih | Suri Dwi Lesmana The publisher of this work supports multiple resolution. The work is available from the following locations: {'doi': '10.18502/ijrm.v24i5.21293', 'member_id': '7770', 'member': 'Knowledge E DMCC', 'container-title': 'International Journal of Reproductive BioMedicine (IJRM)', 'primary-resource': 'https://knepublishing.com/index.php/ijrm/article/view/21293', 'tld': 'knepublishing.com', 'clearbit-logo': '/static/no_logo.svg', 'coaccess': [], 'multiple-resolution': [{'url': 'http://ijrm.ir/article-1-3716-en.html', 'tld': 'ijrm.ir', 'clearbit-logo': '/static/no_logo.svg'}], 'type': 'JOURNAL ARTICLE', 'published_date': '14 July 2026', 'publication': 'International Journal of Reproductive BioMedicine (IJRM)', 'title': 'The role of tumor necrosis factor alpha in regulating CYFRA 21-1 as a potential biomarker for endometriosis: A cross-sectional study', 'name': None, 'id': None, 'location': None, 'display_doi': 'https://doi.org/10.18502/ijrm.v24i5.21293', 'grant_info': None, 'grant_info_funders': None, 'grant_info_funder_ids': '', 'grant_info_type': None, 'multiple_lead_investigators': [], 'multiple_co_lead_investigators': [], 'multiple_investigators': [], 'finances': [], 'project_description': None, 'award_amount': None, 'award_start': None, 'funding_scheme': None, 'internal_award_number': None, 'editors': None, 'authors': 'Nicko Pisceski Kusika Saputra | Samsulhadi Samsulhadi | Hendy Hendarto | Ashon Saádi | Widodo J Pudjirahardjo | I Wayan Arsana | Relly Yanuari | Sri Ratna Dwiningsih | Suri Dwi Lesmana', 'chairs': None, 'supplementary_ids': None} https://doi.org/10.18502/ijrm.v24i5.21293 JSON XML

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