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

TITLE=Lymphangioleiomyomatosis: Searching for potential biomarkers

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1079317

DOI=10.3389/fmed.2023.1079317

ISSN=2296-858X

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 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: Ninety-seven subjects were recruited: 59 (61%) LAM patients, 18 (19%) other cystic lung diseases patients and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from other cystic lung diseases and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465 - 832) ng/mL] than in patients with other cystic lung diseases and healthy controls [medians 360 (314-546) and 427 (365-513) ng/mL respectively (p< 0.0001)]. The area under the curve 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 x VEGF-D + 0.0069 x MMP-2) with higher accuracy than each component alone (area under the curve 0.88 and sensitivity/specificity 79%/87%).
Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.