CDX2 as a Predictive Biomarker Involved in Immunotherapy Response Suppresses Metastasis through EMT in Colorectal Cancer.

Background: Studies have confirmed that Caudal Type Homeobox 2 (CDX2) plays a tumor suppressor role in colorectal cancer (CRC) and as a prognostic and predictive marker for colorectal cancer. The epithelial to mesenchymal transition (EMT) is a transdifferentiation process, providing migratory and invasive properties to cancer cells during tumor progression. However, the role of CDX2 during the activation of EMT in CRC maintains controversial. Aim: To investigate whether CDX2 is associated with EMT in CRC. Methods: Forty-six CRC patients were included in the study. Expressions of CDX2, E-cadherin, and N-cadherin in all CRC patients were detected by IHC. ROC assays were applied to detect cut-off points for IHC scores to distinguish high and low expressions of CDX2 in 46 CRC samples. The prognostic value of CDX2 was statistically analyzed. MTT, Western blot, invasion, and migration assays in vitro were employed to explore the function of CDX2. Results: We observed that high expressions of CDX2 and E-cadherin as well as low expressions of N-cadherin were significantly correlated with favorable prognosis. The levels of CDX2 protein exhibited a positive associated with E-cadherin while negative correlation with N-cadherin. Then, the low expression of CDX2 and high expression of CA199 in combination are positively related with poor prognosis. Overexpression of CDX2 reduced expression of MMP-2 and diminished cell proliferation, invasion, and migration, while knockdown CDX2 enhanced MMP-2 expression and increased cell proliferation, invasion, and migration in HCT-116 cells. CDX2 was correlated with expression of EMT markers. Overexpression of CDX2 suppressed the EMT markers indicating that CDX2 suppresses CRC cell viability, invasion, and metastasis through inhibiting EMT. Finally, we found that the expression of CDX2 was negatively associated with Th1 cells, macrophages, Th2 cells, cytotoxic cells, T cells, and T helper cells. Conclusions: These results indicated CDX2 as prognostic biomarkers involved in immunotherapy response for CRC. CDX2 loss promotes metastasis in CRC through a CDX2-dependent mechanism.

Prognostic value and predictive biomarkers of phenotypes of tumour-associated macrophages in colorectal cancer.

BACKGROUND: The roles of different subtypes of tumour-associated macrophages (TAMs) in predicting the prognosis of colorectal cancer (CRC) remain controversial. In this study, different subtypes of TAMs were investigated as prognostic and predictive biomarkers for CRC. METHODS: Expressions of CD68, CD86 and CD163 were investigated by immunohistochemistry (IHC) and immunofluorescence (IF), and the correlation between the expression of CD86 and CD163 was calculated in colorectal cancer tissues from 64 CRC patients. RESULTS: The results showed that high expressions of CD86+ and CD68+ CD86+ TAMs as well as low expression of CD163+ and CD68+ CD163+ TAMs were significantly associated with favourable overall survival (OS). The level of CD86 protein expression showed a negative correlation with CD163 protein expression. In addition, CD86 protein expression remarkably negatively correlated with tumour differentiation and tumour node metastasis (TNM) stage, while CD163 protein expression significantly positively correlated with tumour differentiation and tumour size. As an independent risk factor, high expression of CD86 TAMs had prominently favourable prognostic efficacy, while high expression of CD68+ CD163+ TAMs had significantly poor prognostic efficacy. CONCLUSIONS: These results indicate that CD86+ and CD68+ CD163+ TAMs as prognostic and predictive biomarkers for CRC.