Plasma High Mobility Group Box 1 (HMGB1), Osteopontin (OPN), and Hyaluronic Acid (HA) as Admissible Biomarkers for Endometriosis

Yunlei Cao, Xishi Liu, Sun‐Wei Guo
Scientific reports · 2019 · vol. 9(1) , pp. 9272 · doi:10.1038/s41598-019-45785-w · PMID:31239500 · PMC6592882 · W2954146243
article OA: gold CC0 ⤵ 24 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This study identified plasma HMGB1, OPN, and HA as admissible biomarkers for endometriosis by evaluating them in mouse models and human patients, correlating their levels with lesion fibrosis and changes after surgical removal.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

The study used a mouse model of endometriosis with serial timepoints and measured plasma HMGB1, OPN, and HA, alongside lesion immunohistochemistry for HMGB1 and related signaling markers (including TLR4/NF-κB axis components, PCNA, IL-33, and RAGE) and lesion fibrosis extent. In mice, plasma levels of HMGB1, OPN, and HA increased with advancing lesions, and OPN/RAGE/IL-33 lesional staining rose progressively whereas HMGB1-related upstream signaling markers (TLR4, p-p65, PCNA) decreased; caveats include that the biomarker performance was assessed using an endometriosis mouse model and that only a small human validation cohort of 30 ovarian endometrioma cases plus 20 controls was included. The same markers were evaluated in humans by lesion staining and plasma testing before and 3 months after surgical removal of all visible lesions, with OPN positively and HMGB1 negatively associated with fibrosis while all three plasma markers correlated positively with lesional fibrosis. This paper is centrally about endometriosis—identifying plasma HMGB1, OPN, and hyaluronic acid (HA) as admissible biomarkers linked to lesional fibrosis and progression.

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Abstract

Identification of biomarkers for endometriosis is an unmet medical need that demands to be fulfilled. In this study, we first used a mouse model of endometriosis and evaluated the potential utility of select biomarkers based on serial observations. Since fibrosis is the end result of lesional development, we chose high mobility group box 1 (HMGB1), osteopontin (OPN), and hyaluronic acid (HA), all three of them have been well documented to be involved in endometriosis and fibrosis, as potential biomarkers. In addition, we performed immunohistochemistry analysis of HMGB1, OPN, and the receptors for HMGB1, such as toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), proliferating cell nuclear antigen (PCNA), interleukin-33 (IL-33), and receptor for advanced glycation endproducts (RAGE)-a pattern recognition receptor, with HMGB1 being its important ligand. We then evaluated the same set of putative markers in 30 women with ovarian endometriomas and 20 without endometriosis, and reevaluated the 3 plasma markers 3 months after the surgical removal of all visible endometriotic lesions. In mouse, the lesional staining levels of OPN, RAGE, and IL-33 were all significantly higher than that of normal endometrium, and increased progressively as lesions progressed. In contrast to HMGB1, TLR4, p-p65 and PCNA staining levels were decreased progressively. In humans, lesional staining levels of OPN correlated positively, while that of HMGB1 correlated negatively with the extent of fibrosis. All three plasma markers correlated positively with the extent of lesional fibrosis. Through this integrated approach, we identified plasma HMGB1, OPN and HA as promising admissible biomarkers for endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Biomarkers Disease Models, Animal Endometriosis HMGB1 Protein Hyaluronic Acid Osteopontin Severity of Illness Index Adolescent Adult Animals Biomarkers Case-Control Studies Endometriosis Endometriosis Female HMGB1 Protein Humans Hyaluronic Acid Mice Mice, Inbred BALB C

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