Dysregulation of the insulin-like growth factor system in non–small cell lung cancer tissue and histologically normal lung tissue in patients with varying degrees of COVID-19 severity.

Abstract

e20046 Background: The COVID-19 pandemic has created new challenges in oncology, particularly in relation to lung cancer. The insulin-like growth factor (IGF) system is a key regulatory complex involved in carcinogenesis, differentiation, proliferation, and inflammatory processes in the lung tissue. Disruptions in this system have been described in non-small cell lung cancer (NSCLC), acute lung injury, and various infectious diseases. The impact of COVID-19 of varying severity on the IGF system in NSCLC patients is poorly understood. The aim of the research was to study the concentrations of insulin-like growth factors (IGF-I, IGF-II) and their carrier proteins (IGFBP-1, IGFBP-2, IGFBP-3) in tumor tissue and in histologically unchanged resection line tissue in patients with NSCLC who previously suffered from COVID-19. Methods: The study included 60 patients with T1-3NхM0 NSCLC (mean age 59.11±2.9 years), divided into two groups: main (n = 30, moderate/severe COVID-19) and control (n = 30, asymptomatic/mild COVID-19), comparable in age and sex. Levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-2 were measured in tumor and resection margin tissues by ELISA. Statistical analysis used Student's t-test and Mann-Whitney U-test; only significant results (p < 0.05) are reported. Results: In the unchanged lung tissue of patients in the main group it was showed a significant increase in IGF-I levels by 1.6 times in men and by 2.2 times in women, as well as in IGF-II levels by 1.8 times in patients of both sexes, compared to the control group. At the same time, the concentration of IGFBP-2 was increased by 1.3-1.9 times, while the levels of IGFBP-1 did not change significantly. In the tumor tissue of patients in the main group, there was a significant increase in IGF-I level, by 1.7 times in men and by 1.3 times in women, as well as in IGF-II level – by 2.0 and by1.7 times, respectively, against a sharp decrease in IGFBP-1, by 2 times in men and by 6 times in women. At the same time three-fold decrease of IGFBP-2 level was noted only in women. Conclusions: Severe COVID-19 infection led to persistent activation of mitogenic signaling pathways in the lung tissue of patients with NSCLC. The observed increase in IGF-I and IGF-II levels, accompanied by a decrease in IGFBP-1 content, creates conditions for enhanced cell proliferation in both tumorous and morphologically intact tissue. The changes in IGFBP-2 content in women only may indicate a sex-specific mechanisms of regulation in this system. The obtained data explain the possible mechanism of the influence of the infection on the lung cancer progression through the prolonged activation of growth signaling pathways.