Integrating SWATH-MS proteomics and transcriptome analysis identifies CHI3L1 as a plasma biomarker for endoscopic resectable gastric cancer

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-datasets joint analysis to screen for stage I GC plasma biomarker. In SWATH-MS assays, we identified 37 up-regulated and 21 down-regulated 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 up-regulated. Only 1 gene, CHI3L1, was characterized as up-regulated in both the datasets consensus list and the SWATH-MS list. Then we detected CHI3L1 level in plasma of a large cohort consisting of 200 participants. The AUC of CHI3L1 in distinguishing stage I GC from others was 0.788. Integrating plasma CHI3L1 level with clinical factors further boosted the AUC into 0.868. In conclusion, we provide a novel strategy for biomarker screening combining recent MS technique with public database analysis and identified plasma CHI3L1 as a potential biomarker for endoscopic resectable GC patients.