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. 2025 Apr;172(4):1379-1386.
doi: 10.1002/ohn.1138. Epub 2025 Jan 20.

Plasma Matrix Metalloproteinase-9 Predicts Intraoperative Experience and Extent of Resection in Vestibular Schwannoma Surgery

Han T N Nguyen  1 , Robert J Macielak  1 , Lisa Zhang  1 , Oliver F Adunka  1 , Kyle C Wu  2 , Yin Ren  1
Affiliations

Plasma Matrix Metalloproteinase-9 Predicts Intraoperative Experience and Extent of Resection in Vestibular Schwannoma Surgery

Han T N Nguyen et al. Otolaryngol Head Neck Surg. 2025 Apr.

Abstract

Objective: To evaluate the predictive value of plasma matrix metalloproteinase-9 (MMP-9) level in determining the extent of tumor resection (EOR) and tumor adherence in vestibular schwannoma (VS) surgery.

Study design: Prospective cohort study.

Setting: Academic referral center.

Methods: Plasma and tumor samples were prospectively collected from patients with nonradiated, sporadic VS undergoing microsurgical resection from July 2022 to June 2023. Plasma MMP-9 levels were measured by enzyme-linked immunosorbent assay, and their association with tumor adherence and postoperative outcomes were evaluated.

Results: Thirty-three patients undergoing microsurgical resection agreed to participate (15 females, median age 54 years old, median tumor size 26.7 mm). A gross total resection (GTR) was performed in 18 patients (55%), and a near-total (NTR)/subtotal resection (STR) in 15 (45%). Tumor size was not significantly different between the GTR and NTR/STR groups (20.7 vs 24.8 mm, P= .185). Intraoperatively, a larger fraction of NTR/STR tumors were highly adherent to the brainstem and/or cranial nerves (93% vs 56%, P = .015). Preoperative plasma MMP-9 was higher in patients who underwent an NTR/STR compared to a GTR (229.9 vs 131.2ng/mL, P = .007). On multivariable logistic regression, preoperative plasma MMP-9 strongly predicted EOR by receiver operating characteristic analysis (area under the curve [AUC] = 0.77 P = .008). Combining plasma MMP-9 and age was an excellent predictor of EOR (AUC = 0.91, P = .0001).

Conclusion: Plasma MMP-9 levels strongly predicted intraoperative tumor adherence and postoperative extent of resection. This could provide crucial preoperative insights into surgical difficulty, potential complications, and the likelihood of gross total tumor removal, enhancing informed decision-making for both physicians/surgeons and patients.

Keywords: MMP‐9; adherence; extent of resection (EOR); vestibular schwannoma.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1.
Figure 1.
MMP-9 is a VS biomarker. (A) Tumor volume. (B) Plasma MMP-9 is enriched in STR. (C) MMP-9 in primary VS culture. (D) MMP-9 is higher in adherent VS. (E) Receiver operating characteristic analysis. *p < 0.05; **p < 0.01. GTR, gross total resection; MMP-9, matrix metalloproteinase-9; PTA, pure-tone average; STR, subtotal resection; VS, vestibular schwannoma.
Figure 2.
Figure 2.
MMP-9 is enriched in VS. (A) Representative immunofluorescence. DAPI, blue; MMP-9, purple; CD31, red; S100B, green. (B) IHC of MMP-9 and CD31. (C) Quantification of staining. DAPI, 4′,6-diamidino-2-phenylindole; GTR, gross total resection; IHC, immunohistochemical; MMP-9, matrix metalloproteinase-9; NTR, near-total resection; STR, subtotal resection; VS, vestibular schwannoma.
Figure 3.
Figure 3.
FRET sensing of MMP-9 activity. (A) FRET measurements of protease-mediated cleavage using plasma from VS patients. (B) Inhibition by MMP-9 specific inhibitors. ELISA, enzyme-linked immunosorbent assay; FRET, fluorescence resonance energy transfer; MMP-9, matrix metalloproteinase-9; VS, vestibular schwannoma.
See this image and copyright information in PMC

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