Department of Allergy, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Respir Res. 2024 Jan 25;25(1):57. doi: 10.1186/s12931-024-02685-6.
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.
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.
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 < 0.0001) and healthy women [49.6 (35.5-78.9) ng/mL, P < 0.0001]. Moesin had an area under the receiver operator characteristic curve (AUC) of 0.929 for predicting LAM diagnosis compared to healthy women (sensitivity 81.0%, specificity 94.6%). The combination of moesin and VEGF-D made a better prediction in differentiating LAM from OCLDs than moesin or VEGF-D alone. Moreover, elevated levels of moesin were related to lymphatic involvement in patients with LAM. Moesin was found negatively correlated with FEV%pred, FEV/FVC, and DLCO%pred (P = 0.0181, r = - 0.3398; P = 0.0067, r = - 0.3863; P = 0.0010, r = - 0.4744). A composite score combining moesin and VEGF-D improved prediction for sirolimus treatment, compared with each biomarker alone.
Higher levels of moesin in serum may indicate impaired lung function and lymphatic involvement in patients with LAM, suggest a more serious condition, and provide clinical guidance for sirolimus treatment.
淋巴管平滑肌瘤病（LAM）是一种易误诊的罕见疾病。血管内皮生长因子 D（VEGF-D）作为最常见的生物标志物，对于 LAM 的诊断和严重程度评估并不完美。
采用同位素标记相对和绝对定量（iTRAQ）方法鉴定细胞骨架蛋白 moesin。收集 84 例 LAM 患者、44 例其他囊性肺疾病（OCLD）患者和 37 名健康对照者的血样和临床资料。通过 ELISA 评估血清 moesin 水平。探讨 LAM 患者 moesin 与淋巴管受累、肺功能和治疗决策的关系。
通过基于蛋白质组学的生物信息学分析鉴定候选蛋白 moesin。LAM 患者血清 moesin 水平高于 OCLD 患者[219.0（118.7-260.5）pg/mL]（P<0.0001）和健康女性[49.6（35.5-78.9）ng/mL]（P<0.0001）。与健康女性相比，moesin 预测 LAM 诊断的受试者工作特征曲线（ROC）下面积（AUC）为 0.929（敏感性 81.0%，特异性 94.6%）。moesin 与 VEGF-D 的联合检测在区分 LAM 和 OCLD 方面优于 moesin 或 VEGF-D 单独检测。此外，LAM 患者 moesin 水平升高与淋巴管受累有关。moesin 与 FEV%pred、FEV/FVC 和 DLCO%pred 呈负相关（P=0.0181，r=-0.3398；P=0.0067，r=-0.3863；P=0.0010，r=-0.4744）。与单独使用每个生物标志物相比，结合 moesin 和 VEGF-D 的复合评分可提高西罗莫司治疗的预测能力。
血清中 moesin 水平升高可能表明 LAM 患者肺功能受损和淋巴管受累，提示病情更严重，并为西罗莫司治疗提供临床指导。
