Relationship Between Farnesoid X Receptor and Macrophage Polarization Status in Colorectal Cancer

Abstract

Objective: Most colorectal cancer patients are insensitive to immunotherapy, which is associated with the polarization state of macrophages in the immune microenvironment. Research indicates that the farnesoid X receptor can modulate the immune microenvironment of colorectal cancer, but its relationship with the polarization status of macrophages requires further investigation. This study aims to investigate the expression of farnesoid X receptor in colorectal cancer, and analyze its correlation with the clinical pathological features of colorectal cancer and the polarization status of macrophages. Methods: Pathological specimens from 31 cases diagnosed with colorectal adenocarcinoma and undergoing surgery at Wuhan Central Hospital between January 2022 and December 2022 were collected. Immunohistochemistry was employed to assess the expression of farnesoid X receptor in tumor cells and tumor stroma. The quantity of CD86-positive and CD206-positive cells in the samples was also measured to reflect the infiltration of M1 and M2 macrophages in the tumor immune microenvironment. Describe the expression of farnesoid X receptor in colorectal cancer tumor cells and tumor stroma, and analyze the relationship between farnesoid X receptor expression and clinical pathological features and macrophage polarization status. Results: The positive rates of farnesoid X receptor expression in tumor cells and tumor stroma were 29.03% and 45.16%, respectively. The expression of farnesoid X receptor in tumor cells was associated with tumor location (P=0.015), with a higher incidence of farnesoid X receptor expression loss in left-sided colon cancer compared to right-sided colon cancer. The expression of farnesoid X receptor in tumor stroma was correlated with macrophage polarization status. The positive expression of farnesoid X receptor in stroma was associated with a higher infiltration of M1-type macrophages (P=0.008) and a higher M1/M2 ratio compared to the farnesoid X receptor expression loss group (P=0.003), suggesting a better response to immunotherapy and a favorable prognosis. Conclusion: Farnesoid X receptor is expressed in both colorectal cancer tumor cells and tumor stroma, showing a close association with the primary site of colorectal cancer and the polarization status of macrophages. The positive expression of farnesoid X receptor in tumor cells is predominantly observed in right-sided colorectal cancer, while the positive expression of farnesoid X receptor in tumor stroma is associated with macrophage polarization towards the M1 phenotype.