Based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) investigation of cere-brospinal fluid (CSF), we prospectively characterized proteins in CSF samples of 36 lung adeno-carcinoma patients, including 19 LM patients and 17 non-LM patients. We identified 290 signifi-cantly differentially expressed proteins (DEPs). In this study, we applied proteomic methods to develop a model to assist diagnosis of LM in lung adenocarcinoma cancer and identified an important biomarker, TSP-2.