Abstract Background Lymphangioleiomyomatosis (LAM) is a rare disease which is easily misdiagnosed. Vascular endothelial growth factor D (VEGF-D), as the most common biomarker, however, is not so perfect for the diagnosis and severity assessment of LAM. Materials and methods The isobaric tags for relative and absolute quantitation (iTRAQ)-based method was used to identify a cytoskeleton protein, moesin. 84 patients with LAM, 44 patients with other cystic lung diseases (OCLDs), and 37 healthy control subjects were recruited for collecting blood samples and clinical data. The levels of moesin in serum were evaluated by ELISA. The relationships of moesin with lymphatic involvement, lung function, and treatment decision were explored in patients with LAM. Results The candidate protein moesin was identified by the proteomics-based bioinformatic analysis. The serum levels of moesin were higher in patients with LAM [219.0 (118.7–260.5) pg/mL] than in patients with OCLDs (125.8 ± 59.9 pg/mL, P
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