Association of serum galectin-3 levels in patients with key clinical and morphological characteristics of colorectal cancer

Introduction. Galectins are a family of β-galactoside-binding proteins involved in the regulation of cell adhesion, proliferation, apoptosis, and the immune response, playing a key role in carcinogenesis. Galectin-3 is the only chimeric protein of the galectin family, whose functional activity is determined by its ability to oligomerize. Increased expression of galectin-3 in tumor tissue and its high serum concentration are associated with colorectal cancer (CRC) progression. However, the clinical, morphological, and prognostic significance of serum galectin-3 levels in this disease remains poorly understood.

Aim. To analyze the association of galectin-3 levels in the blood serum of patients with key clinical, morphological characteristics and prognosis of CRC.

Materials and methods. A total of 210 previously untreated patients with CRC at various stages of the tumor were examined. These patients ranged in age from 31 to 75 years (114 men and 96 women). The control group consisted of 32 healthy donors aged 31 to 67 years (20 women and 12 men). The clinical diagnosis in all patients was confirmed by tumor morphological examination according to the International Histological Classification of Tumors of the Digestive Tract of the World Health Organization (2019). All patients were diagnosed with colon adenocarcinoma of varying degrees of differentiation. Galectin-3 concentrations were determined in serum collected using a standard method before the start of specific treatment using the Human Galectin-3 Quantikine ELISA reagents (R&D Systems, USA) according to the manufacturer’s instructions. Measurements were performed on a BEP 2000 Advance automated enzyme-linked immunosorbent assay (Siemens Healthcare Diagnostics, Germany). Marker levels were expressed as nanograms (ng) per 1 ml of serum. The nonparametric Mann–Whitney and Kruskal–Wallis tests were used to compare parameters and analyze their relationships. Overall survival was analyzed using the Kaplan–Meier method and the nonparametric Cox proportional hazards model. Differences and correlations were considered statistically significant at p < 0.05.

Results. Enzyme-linked immunosorbent assay revealed that baseline pre-treatment serum galectin-3 levels in 210 previously untreated CRC patients ranged widely from 2.6 to 24.7 ng / ml, and the median level (10.7 ng / ml) was statistically significantly higher than that in 32 healthy control donors (8.6 ng / ml) (p = 0.004). ROC analysis data do not support the use of serum galectin-3 levels in the diagnosis of CRC (test sensitivity 39 %, specificity 94 %). The study did not reveal any significant associations between galectin-3 levels and the main clinical and morphological characteristics of CRC. Univariate analysis and Cox regression analysis of galectin-3 levels revealed an unfavorable prognostic significance of this protein in patients with CRC (p = 0.0006 and p = 0.0001, respectively).

Conclusion. A statistically significant increase in serum galectin-3 concentrations was observed in patients with colorectal cancer compared to healthy donors. Despite the lack of associations with clinical and morphological characteristics of the tumor, elevated baseline serum galectin-3 levels in patients with colorectal cancer are significantly associated with a poor overall survival prognosis.