Soluble galectin-4 in colorectal cancer is associated with tumor progression, but is not a predictor of the disease outcome

Background: Galectin-4 is a member of β-galactoside-binding protein family, which is mainly expressed in gastrointestinal epithelial cells and also secreted into the extracellular environment. Studies have shown that galectin-4 is involved in the regulation of proliferation and metastasis of gastric and pancreatic cancer tumor cells. The results of studies on the clinical significance of galectin-4 in colorectal cancer (CRC) are ambiguous: some studies showed its increased expression, associated with aggressive course and unfavorable prognosis, while others showed its decrease. Aim: To analyze the clinical significance of the soluble form of galectin-4 in CRC. Methods: We retrospectively analyzed the medical records of 130 patients (mean age, 61 year) with a verified diagnosis of CRC, who had been examined and treated from 2016 to 2022. Galectin-4 levels were measured in serum obtained by a standard method before the start of specific treatment, by the enzyme-linked immunosorbent assay (ELISA). The control group consisted of 30 healthy donors (mean age, 53 years). Results: The median concentration of galectin-4 in the CRC patients was higher than in the control group (531.9 [350.6–1380] pg/mL vs. 330.1 [173.0–566.4] pg/mL, p = 0.0004). The ROC analysis demonstrated maximum sensitivity and specificity of the test (66% and 67%, respectively) at a threshold value of 426.3 pg/mL (area under the curve 0.706 with 95% confidence interval 0.594–0.817; p = 0.0005). The galectin-4 levels were higher at advanced stages of the disease (p = 0.002) and in the presence of distant metastases (p 0.0001). Cox regression analysis showed that tumor size and distant metastases were independent prognostic factors (hazard ratio (HR) = 3.87; p = 0.0439; HR = 720.4; p = 0.0062, respectively) associated with decreased survival. Galectin-4 is not a prognostic marker of CRC (HR = 2.434; p = 0.079). Conclusion: The amounts of the soluble galectin-4 are associated with tumor progression, indicating a possible tumor-promoting function of this protein. However, its diagnostic value remains limited, as the method of serum galectin-4 determination has shown insufficient sensitivity and specificity for its routine use for the diagnosis of CRC. According to the results of univariate and multivariate analyses, serum galectin-4 is not a significant prognostic marker of CRC.