BACKGROUND Congenital Pulmonary Airway Malformation (CPAM) has an estimated prevalence between 0.87 and 1.02/10,000 live births and little is know about their pathogenesis. To improve our knowledge on these rare malformations, we analyzed the cellular origin of the two most frequent CPAM, CPAM types 1 and 2, and compared these malformations with adjacent healthy lung and human fetal lungs. METHODS We prospectively enrolled 21 infants undergoing surgical resection for CPAM. Human fetal lung samples were collected after termination of pregnancy. Immunohistochemistry and proteomic analysis were performed on laser microdissected samples. RESULTS CPAM 1 and 2 express mostly bronchial markers, such as cytokeratin 17 (Krt17) or α-smooth muscle actin (ACTA 2). CPAM 1 also expresses alveolar type II epithelial cell markers (SPC). Proteomic analysis on microlaser dissected epithelium confirmed these results and showed distinct protein profiles, CPAM 1 being more heterogeneous and displaying some similarities with fetal bronchi. CONCLUSION This study provides new insights in CPAM etiology, showing clear distinction between CPAM types 1 and 2, by immunohistochemistry and proteomics. This suggests that CPAM 1 and CPAM 2 might occur at different stages of lung branching. Finally, the comparison between fetal lung structures and CPAMs shows clearly different protein profiles, thereby arguing against a developmental arrest in a localized part of the lung.

中文翻译：

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蛋白质组学分析揭示了对先天性肺气道畸形的新见解。

背景技术先天性肺气道畸形（CPAM）的患病率估计在0.87至1.02 / 10,000之间，对其发病机理知之甚少。为了提高我们对这些罕见畸形的认识，我们分析了两种最常见的CPAM（CPAM 1型和2型）的细胞起源，并将这些畸形与邻近的健康肺和人胎肺进行了比较。方法我们前瞻性招募了21例接受CPAM手术切除的婴儿。终止妊娠后收集人胎肺样品。免疫组织化学和蛋白质组学分析是在激光显微切割的样品上进行的。结果CPAM 1和2主要表达支气管标志物，例如细胞角蛋白17（Krt17）或α-平滑肌肌动蛋白（ACTA 2）。CPAM 1还表达II型肺泡上皮细胞标记（SPC）。显微解剖的上皮的蛋白质组学分析证实了这些结果，并显示出不同的蛋白质谱，CPAM 1的异质性更强，并且与胎儿支气管有相似之处。结论这项研究提供了CPAM病因学的新见解，通过免疫组织化学和蛋白质组学显示了CPAM 1型和2型之间的明显区别。这表明CPAM 1和CPAM 2可能发生在肺分支的不同阶段。最后，胎儿肺结构与CPAM之间的比较显示出明显不同的蛋白质谱，从而争论了肺局部区域的发育停滞。结论这项研究提供了CPAM病因学的新见解，通过免疫组织化学和蛋白质组学显示了CPAM 1型和2型之间的明显区别。这表明CPAM 1和CPAM 2可能发生在肺分支的不同阶段。最后，胎儿肺结构与CPAM之间的比较显示出明显不同的蛋白质谱，从而争论了肺局部区域的发育停滞。结论这项研究提供了CPAM病因学的新见解，通过免疫组织化学和蛋白质组学显示了CPAM 1型和2型之间的明显区别。这表明CPAM 1和CPAM 2可能发生在肺分支的不同阶段。最后，胎儿肺结构与CPAM之间的比较显示出明显不同的蛋白质谱，从而争论了肺局部区域的发育停滞。