Incremental Diagnostic Value of the Plasma Kynurenine/Tryptophan Ratio for Deep Infiltrating Endometriosis and Its Correlation With Eutopic Endometrial Matrix Metalloproteinase-9 Expression: A Single-Center Prospective Study

Hubin Xu, Haimin Jiang, Chenmei Ma
In: Clinical and Experimental Obstetrics & Gynecology · 2026 · vol. 53(5) · doi:10.31083/ceog47790 · W7162800654
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study found that the plasma kynurenine/tryptophan ratio offers incremental diagnostic value for deep infiltrating endometriosis and correlates with endometrial MMP-9 expression.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 ⓘ

This single-center prospective diagnostic study evaluated whether plasma kynurenine/tryptophan ratio (KTR), measured by LC-MS/MS before surgery, adds independent diagnostic value for deep infiltrating endometriosis (DIE) beyond a baseline pathway including symptoms, signs, CA-125, and imaging, using surgical pathology as the gold standard. KTR differed between DIE and non-DIE groups, showed an association with higher ENZIAN stage, and improved discrimination when added to the baseline model (AUC 0.79 to 0.83) with improved calibration and net benefit on decision curve and reclassification analyses; KTR also correlated independently and positively with eutopic endometrial MMP-9 expression assessed by IHC. The paper’s main caveats are that it is single-center and uses only preoperative sampling/paired eutopic MMP-9 correlation rather than a systematic mechanistic investigation. This paper is centrally about endometriosis — specifically, it focuses on plasma KTR as an incremental diagnostic biomarker for deep infiltrating endometriosis and its correlation with eutopic endometrial MMP-9.

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Abstract

Background: Surgery for deep infiltrating endometriosis (DIE) is complex, and current clinical imaging has limited ability to identify and stratify atypical lesions. The kynurenine/tryptophan ratio (KTR) reflects immunometabolic activation, and matrix metalloproteinase-9 (MMP-9) is associated with tissue invasion. Methods: This was a single-center prospective study, with pathology as the gold standard. Three analysis populations were defined. KTR was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and MMP-9 by immunohistochemistry (IHC) derived histochemical score (H-score). Multivariable regression, DeLong comparison, calibration and decision curves, and nested F test were used. Results: Compared with controls, KTR differed in the DIE and non-DIE groups, with β_diff = 0.28/0.15 (both p_adj < 0.05). Each 1 SD increase in natural log transformed KTR (lnKTR) was associated with higher ENZIAN stage (OR_perSD = 1.62, p < 0.001). After KTR was added to the baseline model, the area under the receiver operating characteristic curve (AUC) increased from 0.79 to 0.83 (ΔAUC = 0.04, 95% CI: 0.02–0.07, p = 0.003). Net benefit increased across the 10%–30% threshold range, and calibration improved from α = –0.127, β = 0.861 to α = –0.039 and β = 0.946. Among imaging suspected but atypical subjects, net correct reclassification was +14 for events and +17 for non-events. KTR was independently and positively associated with MMP-9 (β_std = 0.29, 95% CI: 0.15–0.43, p < 0.001), with ΔR2 = 0.04 (F = 11.882, p < 0.001). Conclusions: KTR provides an independent and translatable diagnostic increment on current pathways and is associated with eutopic endometrial MMP-9, supporting coupling between systemic immunometabolism and local remodeling. These findings support its use for preoperative stratification and optimization of surgical planning.

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Outcome instruments

Enzian

Condition tags

endometriosisdie_deep_infiltrating

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (24)

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