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

Abstract

Abstract Background: The identification of proteins involved in the occurrence of early intestinal-type gastric cancer (EIGC) may provide valuable insights into the pathogenesis of intestinal gastric cancer. Methods: 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), and 21 healthy controls. The prognostic values of the five genes were validated in the transcriptome data by survival analysis. Results: A total of 4,028 proteins were identified using DIA-MS, with fold change> 1.5 times as a significant difference, and a total of 177 different proteins were screened. Among them, 113 proteins were significantly up-regulated in EIGC tissues, 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 quantitative results of DIA-MS. Among them, p62/SQSTM1 may undergo nuclear-cytoplasmic transfer. The expression of noncancerous gastric mucosa was different from LGIN and EIGC, while LGIN was similar to EIGC. The five protein coding genes were associated with intestinal-type gastric cancer survival and differentially expressed in different stages. Conclusion: The study successfully identified differentially expressed proteins between EIGC and NGC, which may provide valuable insights into the mechanism of intestinal-type gastric cancer. Additionally, the study highlights the risk of some LGIN developing into invasive gastric cancer, which warrants further attention.