Data-independent acquisition (DIA) mass spectrometry reveals related proteins involved in the occurrence of early intestinal-type gastric cancer.

Abstract

Identifying proteins associated with the onset of early intestinal-type gastric cancer (EIGC) can yield valuable insights into the pathogenesis of this specific subtype of gastric cancer. Data-independent acquisition mass spectroscopy (DIA-MS) was utilized to identify the differential protein between 10 cases of EIGC and atrophic gastritis with intestinal metaplasia (NGC). The expressions of IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were verified by immunohistochemistry (IHC) in 20 EIGC samples, 17 gastric low-grade intraepithelial neoplasia (LGIN) samples, and 21 healthy controls. The prognostic values of the five genes were validated in the transcriptome data by survival analysis. A total of 4,028 proteins were identified using DIA-MS and a total of 177 differential proteins were screened with log2(fold change) > 1.5. Among them, 113 proteins were significantly up-regulated, and 64 proteins were significantly down-regulated in EIGC tissues. IHC results showed that proteins IPO4, TBL1XR1, p62/SQSTM1, PKP3, and CRTAP were highly expressed in the cytoplasm of EIGC and LGIN, which was consistent with the results of DIA-MS. Among them, p62/SQSTM1 may undergo nuclear-cytoplasmic transfer. The five protein-coding genes were associated with intestinal-type gastric cancer survival and exhibited differential expression across various disease stages. The study successfully identified differentially expressed proteins between EIGC and NGC, providing potential biomarkers and valuable insights into the mechanism underlying intestinal-type gastric cancer.