AUTHOR=Terraneo Silvia , Lesma Elena , Ancona Silvia , Imeri Gianluca , Palumbo Giuseppina , Torre Olga , Giuliani Lisa , Centanni Stefano , Peron Angela , Tresoldi Silvia , Cetrangolo Paola , Di Marco Fabiano 

TITLE=Exploring the Role of Matrix Metalloproteinases as Biomarkers in Sporadic Lymphangioleiomyomatosis and Tuberous Sclerosis Complex. A Pilot Study

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.605909

DOI=10.3389/fmed.2021.605909

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> Lymphangioleiomyomatosis can develop in a sporadic form (S-LAM) or in women with tuberous sclerosis complex (TSC). The matrix metalloproteinases (MMPs) are extracellular matrix-degrading enzymes potentially involved in cystic lung destruction, and in the process of migration of LAM cells. The aim of the study was to explore the role of MMP-2 and MMP-7, such as vascular endothelial growth factor (VEGF) -C and -D in women with LAM, including patients with minor pulmonary disease (i.e., &lt;10 lung cysts), and TSC with or without LAM.</p><p><bold>Methods:</bold> We evaluated 50 patients: 13 individuals affected by S-LAM, 20 with TSC-LAM, of whom six with minor pulmonary disease, and 17 with TSC without pulmonary involvement. Sixteen healthy women were used as controls.</p><p><bold>Results:</bold> MMP-2 resulted higher in LAM compared to healthy volunteers, and TSC patients (<italic>p</italic> = 0.040). MMP-7 was higher in TSC-LAM patient, with even greater values in patients with TSC-LAM minor pulmonary disease, than in S-LAM patients, and in controls (<italic>p</italic> = 0.001). VEGF-D level was lower than 800 pg/mL in all healthy controls and resulted higher in S-LAM and TSC-LAM than in TSC patients and controls (<italic>p</italic> &lt; 0.001). VEGF-C values were not statistically different in the study population (<italic>p</italic> = 0.354). The area under ROC curves (AUCs) of MMP-2, and MMP-7 for predicting LAM diagnosis were of 0.756 ± 0.079 (<italic>p</italic> = 0.004), and 0.828 ± 0.060 (<italic>p</italic> &lt; 0.001), respectively. Considering only patients with TSC, the AUCs for MMP-2, and MMP-7 in predicting LAM were 0.694 ± 0.088 (<italic>p</italic> = 0.044), and 0.713 ± 0.090 (<italic>p</italic> = 0.027), respectively.</p><p><bold>Conclusions:</bold> Our data suggest that MMP-2 and MMP-7 could be promising biomarkers for LAM diagnosis.</p>