Clinical significance of soluble forms of galectins in bone tumors in children

Introduction. Galectins are glycan-binding proteins containing one or two carbohydrate domains and performing many biological functions. It has been established that galectins synthesized by tumor tissue have the ability to autostimulate and paracrine stimulate cells of the microenvironment. Literature data indicate that changes in galectin production and secretion are observed in many types of malignant neoplasms and often contribute to their rapid progression. Interestingly, there is increasing evidence that a family of β-galactoside-binding lectins, known as galectins, plays a key role in the adhesion of circulating tumor cells to the vascular endothelium, contributing to the dissemination of the tumor process. For a number of solid tumors, the role of some galectins, especially galectin-3, has been studied and described fairly well, while in tumors of the bone system, the clinical and laboratory significance of proteins of this family has not yet been determined.

Purpose of the study – comparative analysis of the content of galectins-1, -3, -4, -7, -9 in the blood serum of bone tumors and healthy donors in pediatric oncology practice, connection with the main clinical and morphological characteristics of the disease and determination of their diagnostic potential.

Materials and methods. The retrospective study included 95 patients with bone tumors: malignant (n = 66), benign (n = 25) and borderline (n = 4), who were treated at the N.N. Blokhin National Medical Research Centre of Oncology, Ministry of Health of Russia. The clinical and radiological diagnosis of the tumor was confirmed by the data of a morphological study of the tumor according to the International Histological Classification of Bone Tumors (World Health Organization, 2020). The concentration of galectins-1, -3, -4, -7, -9 was determined in blood serum obtained according to standard methods before the start of specific treatment, using reagent kits for enzyme-linked immunosorbent assays. The obtained data were processed using the GraphPad Prizm 10.0 program. When comparing indicators and analyzing their relationships, nonparametric Mann–Whitney and Kruskal–Wallis tests were used. Analysis of the information content of the diagnostic method by assessing its sensitivity and specificity was carried out by constructing ROC curves and calculating the area under them (AUC). Correlation analysis was carried out by determining the Spearman correlation coefficient. Differences and correlations were considered statistically significant at p < 0.05.

Results. It was found that the median galectin-3 content in the control group was 6.69 (4.15–9.94) ng/ml, which is significantly lower than in patients with bone tumors – 7.85 (5.85–11.75) ng/ml (p = 0.033). Significant changes in content were detected for galectin-9. In patients with bone tumors, the median concentration of galectin-9 is 5.35 (4.28–6.89) ng/ml, which is statistically significantly lower compared to the control group – 7.37 (6.09–8.870) ng/ml (p = 0.001). The ROC-analysis showed that despite significant changes in the content of galectin-3 and galectin-9 in the blood serum of patients with bone tumors, the study of their concentrations does not allow using the data obtained in the clinic for diagnostic purposes. The analysis showed that for galectin-1 and galectin-7 there is no change in their concentration during the development of benign and malignant bone tumors. For galectin-3, a significant increase in its content was shown in the case of the development of malignant bone tumors, while for galectin-4 similar patterns were noted in the development of benign bone tumors. The content of galectin-9 was significantly reduced in patients with both benign and malignant tumors compared to controls. Correlation analysis showed that in the control group the content of galectin-9 inversely correlates with the level of galectin-1 and galectin-7 (r = –0.533; p = 0.019 and r = –0.473; p = 0.041, respectively). In the group of patients with bone tumors the content of galectin-1 directly correlates with the level of galectin-3 (r = 0.360; p = 0.004), and the level of galectin-7 with galectin-9 (r = 0.420; p = 0.001), which indicates a change balance of the content of these proteins during the development of tumor pathology of skeletal bones.

Conclusion. Our work revealed changes in the balance of galectins-1 , -3, -4, -7, -9 in the blood serum of children with tumors of the musculoskeletal system. Despite the ambiguous results, galectins, due to their widespread occurrence in the human body, remain promising molecules for use in clinical, laboratory and scientific practice as biological markers. However, further studies are needed to confirm their clinical significance.

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