Abstract:
Objective Leptomeningeal metastasis (LM) from lung adenocarcinoma is a serious disease caused by lung adenocarcinoma cells metastasizing to the meninges. This study aimed to analyze the proteome changes in the cerebrospinal fluid of LM patients by label-free liquid chromatography-mass spectrometry (LC-MS/MS), and identifying the potential diagnostic markers.
Methods Thirty LM patients (patient group), and 30 non-inflammatory neurological-disease patients (control group) were selected from those who visited Tianjin Huanhu Hospital, from 2019 January to 2021 December. The LC-MS/MS was used to detect the proteome in cerebrospinal fluid; Gene Ontology (GO) was used to analyze the biological process (BP) and cellular composition (CC), while their biological functions were predicted by Kyoto encyclopedia of genes and genomes (KEGG) analysis. The above mentioned analysis was certified by rate scatter turbidimetry, immune transmission turbidimetry, and enzyme linked immunosorbent assay (ELISA) in cerebrospinal fluid, while the diagnostic efficiency was analyzed by receiver operating characteristic (ROC) curve.
Results Thirteen and six proteins in the cerebrospinal fluid of the patient group were significantly up- and down-regulated, respectively, when compared with the control group. Bioinformatics analysis revealed the acute inflammatory response and response to wounding, to be the major enriched biological process, while the cell components such as extracellular membrane-bounded organelles, extracellular exosome and extracellular vesicle, were changed. The significantly up-regulated alpha-1-microglobulin (AMBP), complement C1QC/2/7/8B, IgG, peptidoglycan recognition protein 2 (PGLYRP2), and serum amyloid A4 (SAA4) (all P<0.05) in cerebrospinal fluid, were identified by rate scatter turbidimetry, immune transmission turbidimetry, and ELISA assay. The area under curve (AUC), sensitivity, and specificity of C2+PGLYRP2 were 0.97, 83.33%, and 96.67%, respectively.
Conclusions The cerebrospinal fluid immune response is significantly up-regulated in patients with meningeal metastases of lung adenocarcinoma, with C2+PGLYRP2 being a potential adjuvant diagnostic marker.