Screening Proteins Associated with the Development and Progression of Colorectal Cancer by LC-MS/MS

Abstract

Background: Colorectal cancer (CRC) is a common disease worldwide. Most patients are diagnosed at advanced stages, resulting in a poor prognosis. Therefore, early detection is essential for improving the prognosis of CRC and reducing social burden. In this study, the mechanisms underlying CRC development and progression were evaluated. Methods: Liquid chromatography-mass spectrometry was used to analyze proteins in grade 2 and grade 3 CRC tissues and their corresponding paracancerous tissues. Differentially expressed proteins (DEPs) between CRC tissues and paracancerous tissues as well as those between grade 2 and grade 3 tissues were identified. Functional and pathway enrichment analyses of the DEPs in each comparison were performed. Finally, western blotting was performed to validate the expression levels of critical proteins. Results: In total, 227, 103, and 181 DEPs were identified between grade 2 cancer tissues and paracancerous tissues, between grade 3 cancer tissues and paracancerous tissues, and between grade 2 and grade 3 cancer tissues, respectively. Functional analyses showed that these DEPs are involved in eukaryotic initiation factor 2 signaling, integrin-linked kinase signaling, the tricarboxylic acid cycle, liver X receptor/retinoid X receptor signaling, and phosphoinositol-3 kinase/AKT signaling pathways varied at different tumor stages. Western blotting showed that the protein expression levels of periostin and serpin H1 were significantly higher (p < 0.05) and calponin-1 levels were significantly lower (p < 0.05) in CRC tissues than in paracancerous tissues. Conclusions: Periostin, serpin H1, and calponin-1 are novel candidate diagnostic and prognostic targets for CRC.