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Integrating SWATH-MS Proteomics and Transcriptome Analysis Identifies CHI3L1 as a Plasma Biomarker for Early Gastric
Li Min1, Shengtao Zhu1, Rui Wei1
1Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, P. R. China.
Abstract:
Early diagnosis of gastric cancer (GC) provides patients opportunities for minimally invasive endoscopic resection. Here, we developed a new strategy integrated the state-of-the-art sequential windowed acquisition of all theoretical fragment ion (SWATH) mass spectra (MS) with multi-dataset joint analysis to screen for the stage-I GC plasma biomarker. In SWATH-MS assays, we identified 37 upregulated and 21 downregulated proteins in GC plasma. In the mRNA database analysis, 633 genes were identified as differentially expressed genes in at least 4 out of 5 datasets, but there were only 94 genes identified as upregulated. Only 1 gene, CHI3L1, was characterized as upregulated in both the dataset consensus list and the SWATH-MS list. Then, we detected the CHI3L1 level in the plasma of a large cohort consisting of 200 participants. The area under the ROC curve (AUC) of CHI3L1 in distinguishing GC from others was 0.788. Integrating the plasma CHI3L1 level with clinical factors further boosted the AUC to 0.887. In conclusion, we provide a novel strategy for biomarker screening, combining recent MS techniques with public database analysis, and identified plasma CHI3L1 as a potential biomarker for patients with endoscopically resectable GC.
