Induction of different pathways of complement system protein activation in gastric adenocarcinoma

Background. The increase in the prevalence of cancer, including gastric adenocarcinoma, prompts the search for prognostic predictors of this dangerous pathology. It is known that genome instability, which is related to cellular transformation, has increased sharply after the SARS-CoV-2 pandemic, and especially in patients with the post-COVID-19 syndrome symptom complex. There is pronounced clinical heterogeneity in the presence of the stage and prevalence of the tumor process and pronounced polymorphism of the immune disordersʼ spectrum associated with a certain age of patients. It is known that chronic inflammation is a prerequisite for the oncological process progression. Today, for the treatment of gastric adenocarcinoma, methods of targeted immunotherapy limited to a certain number of control points are used in complex therapy. To improve approaches to tumor immunotherapy, it is advisable to further study disorders of immunoreactivity factors that can contribute to the development of inflammatory processes induction. Purpose – is to assess the content of the central component C3 and the multifunctional component C4 and the complement system total hemolytic activity in different age groups of patients with comorbid post-COVID-19 syndrome and gastric adenocarcinoma of prevalence varying degrees to predict the oncological process and justify individual approaches for targeted immunocorrection. Materials and Methods. We examined 51 patients with gastric adenocarcinoma of various stages and prevalence. Three age groups of patients were distinguished: group 1 (n = 17, mean age 51.5 ± 3.6 years); group 2 (n = 12, mean age 64.1 ± 2.5 years); group 3 (n = 22, mean age 73.7 ± 3.1 years). Methods used: immunoturbidimetry (complement C3 and C4 components concentration); spectrophotometry (hemolytic activity of complement, concentration of circulating immune complexes (CICs) and DAMPs cytotoxic fractions). Results. Complement components C3 and C4, as the main effectors of innate immunity; differently affect the tumor process from its inhibition to activation. In all age groups of patients with different stages of gastric adenocarcinoma, a significant increase in the C3 component was found, which indicated the alternative complement pathway activation and the presence of an inflammatory process that contributes to the oncological pathology development. In the group 2, an increase in the concentration of C3 and a decrease in the concentration of C4 component due to its consumption were found, which is a negative factor; and an increase in the concentration of C4 (group 1 and 3) is a positive prognostic factor. However, all patients showed a decrease in the functional hemolytic activity of complement. In group 2, a significant increase in the DAMPs oligonucleotide fraction was found due to the accumulation of cellular debris against the background of the inflammatory reaction. Conclusions. Activation of complement components against the background of a decrease in hemolytic activity indicates incomplete final stages of innate immunity cytolytic reactions, and it is precisely due to the accumulation of CICs and an increase in the DAMPs oligonucleotide fraction that it contributes to the inflammatory process development in patients with different stages and prevalence of gastric adenocarcinoma depending on age. The results obtained may be the basis for the development of the identified checkpoints immunocorrection.