B7-H4 is a potential diagnostic and prognostic biomarker in colorectal cancer and correlates with the epithelial-mesenchymal transition

Abstract

BACKGROUND: As a negative co-stimulatory molecule of the B7 family, B7-H4 has recently attracted increased attention. However, the clinical value of B7-H4 in colorectal cancer (CRC) remains controversial and requires further investigation. This study aimed to investigate the role of B7-H4 in the clinical diagnosis and survival prognosis of CRC. METHODS: The relationships between B7-H4 expression, immune cell infiltration, epithelial-mesenchymal transition (EMT), clinicopathological features, and survival prognosis were determined through the TCGA database and verified in a large CRC cohort (n = 1118). RESULTS: The results showed the level of B7-H4 mRNA expression was significantly increased in the CRC tumor tissues compared with normal tissues (P < 0.001). Immunohistochemistry showed that B7-H4 protein expression was also up-regulated in CRC. The positive rate of B7-H4 in CRC tumor tissues was 76.38%, which was significantly higher than that in non-tumor tissues (P < 0.001). Overexpression of B7-H4 was positively correlated with lymph node metastasis, advanced TNM stage, and poor tumor differentiation (P = 0.012; 0.009; 0.014). Prognostic analysis showed high B7-H4 expression was associated with significantly shorter OS. Multivariate analysis demonstrated the risk of death in CRC patients with high B7-H4 expression is 1.487 times that of low B7-H4 expression. In addition, B7-H4 expression was negatively correlated with the epithelial marker E-cadherin (P < 0.001) and positively correlated with the mesenchymal marker vimentin (P < 0.001) in CRC tissues. However, B7-H4 expression was not associated with the immunosuppressive microenvironment in CRC. CONCLUSION: B7-H4 may represent a potential biomarker for the diagnosis and prognosis of CRC and enhance CRC invasion by promoting EMT.