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. 2023 Feb 2:10:1079317.
doi: 10.3389/fmed.2023.1079317. eCollection 2023.

Lymphangioleiomyomatosis: Searching for potential biomarkers

Eva Revilla-López  1   2 , Victoria Ruiz de Miguel  3 , Manuel López-Meseguer  1 , Cristina Berastegui  1 , Meritxell Boada-Pérez  3 , Alberto Mendoza-Valderrey  3 , Marta Arjona-Peris  1 , Marta Zapata-Ortega  1 , Victor Monforte  1   4 , Carlos Bravo  1   4 , Antonio Roman  1   4 , Susana Gómez-Ollés  2   3   4 , Berta Sáez-Giménez  1   2   5
Affiliations

Lymphangioleiomyomatosis: Searching for potential biomarkers

Eva Revilla-López et al. Front Med (Lausanne). .

Abstract

Background: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers.

Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination.

Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465-832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314-546) and 427 (365-513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (-6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%).

Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.

Keywords: VEGF-D; biomarkers; diagnose; lymphangioleiomyomatosis; metalloproteinases; serum.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Subjects enrolled in the study.
FIGURE 2
FIGURE 2
Comparison of serum metalloproteinase-2 (MMP-2) and vascular endothelial growth factor-D (VEGF-D) levels between lymphangioleiomyomatosis (LAM) patients, other cystic lung diseases (OCLD), and healthy controls. Solid lines indicate median and interquartile range (IQR).
FIGURE 3
FIGURE 3
Comparison of serum metalloproteinase-2 (MMP-2) and vascular endothelial growth factor-D (VEGF-D) levels between lymphangioleiomyomatosis (LAM) patients, LAM lung transplantation (LT) patients, other cystic lung diseases (OCLD), and healthy controls. Solid lines indicate median and interquartile range (IQR).
FIGURE 4
FIGURE 4
(A) Receiver operating characteristic (ROC) curves for metalloproteinase-2 (MMP-2) (green line) and vascular endothelial growth factor-D (VEGF-D) (blue line). (B) ROC curves of MMP-2 (green line) and the combination of MMP-2 and VEGF-D (red line). (C) ROC curves of VEGF-D (blue line) and the combination of MMP-2 and VEGF-D (red line).
FIGURE 5
FIGURE 5
Classification of lymphangioleiomyomatosis (LAM) patients based on median FEV1% pred. higher or lower than 73.5%.
See this image and copyright information in PMC

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