The early predictive effect of low expression of the ITGA4 in colorectal cancer

Background: The early diagnosis of colorectal cancer (CRC) is very important for the prognosis of patients. It has been suggested that the cytosine-phosphate-guanine (CpG) island of itga4 is highly methylated in colorectal adenoma cell lines AA/C1, Vaco 235 and so on. So the purpose of our study is to explore the diagnostic accuracy and related mechanism of integrin alpha 4 (ITGA4) in early CRC. Methods: The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between the expression of ITGA4 and the clinicopathological features and the overall survival rate of the disease. Then, the interaction protein and function enrichment region of ITGA4 were analyzed. Finally, the infiltration of related immune cells was analyzed. Results: Compared with normal tissues, the expression of ITGA4 in colon adenocarcinoma and rectum adenocarcinoma (COAD-READ) tumor tissues was lower (P<0.05). The overall survival rate of COAD-READ patients with low ITGA4 level was lower than that of patients with high ITGA4 expression (P<0.05), and expression of ITGA4 had a more significant predictive effect in the early stage of tumor development. The results of protein network and enrichment analysis suggested that ITGA4 was closely related to ITGB2 and might be involved in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of inflammatory bowel disease (IBD), which was verified by another independent sequence. In terms of immune infiltration, the expression level of ITGA4 was positively correlated with the infiltration level of intestinal macrophages (Th17), immature dendritic cells (IDC), dendritic cells (DC), mast cells, and eosinophils in COAD-READ, and significantly negatively correlated with CD56(bright) natural killer (NK) cells. Conclusions: The low expression of ITGA4 was related to the poor prognosis of COAD-READ. Findings showed that ITGA4 might participate in the inflammatory reaction and inflammatory tumor transformation process in the carcinogenesis of IBD, and that ITGA4 was related to the infiltration of immune cells, macrophages, syndactyls, and CD56(bright) NK cells. The expression of ITGA4 could be used as an early predictor of CRC. However, the mechanism of ITGA4 promoting tumor progression in CRC still needs further research.