Rationale importance of integrated determination of the level of CYFRA 21-1 and the receptors CXCR1, CXCR2, CD44v6 in the blood of patients with early-stage non-small cell lung cancer for predicting the tumor progression risk

Abstract

Only 60-70 % patients with stage I and 35-40 % with stage II of non-small cell lung cancer (NSCLC) overcome the 5-year survival. The reason for such a high mortality rate is almost always a disease recurrence due to the presence of hidden metastases. This indicates a different course of the disease within one stage. There is a need to develop indicators that would allow predicting the tumor progression in patients at the early tumor development stages in order to correctly build the strategy and tactics of their treatment.The objective of the study is to find and substantiate the possibility of using the laboratory parameters characterizing the level of blood proteins involved in carcinogenesis when predicting the NSCLC progression in patients with early disease stages.In 1250 patients (839 men and 411 women) who were first diagnosed with NSCLC in the early stages (I and II), the duration of the recurrence-free period after treatment was analyzed according to the one-year observation results. In 103 patients (56 ± 22.5 years), the level of CYFRA 21-1, SCC, TPA, M2 of pyruvate kinase, chemokines CXCL5, CXCL8 and the concentration of HIF1a and hyaluronic acid in blood serum were determined by the enzyme immunoassay and that of the receptors CXCR1, CXCR2, CD44v6 in blood granulocytes, lymphocytes and monocytes - by flow cytometry. 62 persons had stage I (G1 - 20, G2 - 23, G3 - 19) and 41 - stage II (G1 - 14, G2 - 15 and G3 - 12).Based on the results of the one-year observation and the graphic analysis of Kaplan-Meier, the groups of low (stage I, G1-2 + stage II, G1) and high (stage I, G3 + stage II, G2-3) risk of tumor progression were identified. In high-risk patients, compared with low-risk patients, the level of CYFRA 21-1, the fluorescence intensity of the receptor CXCR1 in granulocytes, the relative content of the receptor CXCR2 in lymphocytes and the receptor CD44v6 in monocytes were higher (p< 0.05). With their participation, according to the results of logistic regression analysis, an equation was constructed, the calculation of which allows predicting the risk of tumor recurrence. The threshold for the equation is 0.467. The sensitivity of the forecasting model is 84.8 %, the specificity is 84.2 %, the predictive values of positive and negative results are 81.2 and 87.3 % respectively.The study results showed that a set of laboratory parameters, including blood CYFRA 21-1 level in combination with CXCR1, CXCR2, CD44v6 can be used in patients with early stages of NSCLC to assess the risk of tumor progression.