Serum total bile acid correlates with macrophage-related immune features in colorectal cancer patients after cholecystectomy.

Cholecystectomy has been associated with an elevated risk of colorectal cancer (CRC), potentially mediated by alterations in bile acid metabolism. This single-center retrospective case-control study aimed to investigate the clinical significance of serum total bile acid (TBA) levels in patients with CRC after cholecystectomy, their association with farnesoid X receptor (FXR) expression, and their relationship with tumour-associated macrophage (TAM)-related immune features within the tumour microenvironment. A total of 216 post-cholecystectomy patients with CRC and 209 post-cholecystectomy controls without CRC were enrolled in the study. Serum TBA levels were quantified and statistically compared between the two groups. Immunohistochemical analysis was performed on tumour tissues to assess FXR expression and TAM markers (CD163, CD68). Pearson correlation analysis was performed to examine the associations among serum TBA levels, FXR expression, and TAM-related immune features. Serum TBA levels were significantly higher in the CRC group (8.74 ± 4.45 µmol/L) compared to the Control group (4.61 ± 2.90 µmol/L). ROC analysis showed an AUC of 0.79 (95% CI: 0.74-0.83). Elevated TBA levels were associated with advanced disease features, including higher TNM stage and lymph node metastasis. Immunohistochemistry revealed increased FXR expression and a higher proportion of CD163+ TAMs in the high TBA group, while the proportion of CD68+ TAMs was reduced. Pearson correlation analysis showed that TBA levels were positively correlated with FXR+ cells (r=0.57, P < 0.001) and CD163+ macrophages (r=0.51, P < 0.001), and negatively correlated with CD68+ macrophages (r=-0.44, P < 0.001). Elevated serum TBA levels were associated with increased FXR expression and altered TAM characteristics in CRC after cholecystectomy. These findings indicate that TBA levels may represent a biomarker associated with CRC-related clinicopathological and immune characteristics.