Significance of the cytokeratin-19 fragment and CXCR1, CXCR2 receptors in the blood for prediction of the relapse-free survival of patients with stage III non-small cell lung cancer

Abstract

Stage III non-small cell lung cancer (NSCLC) is a heterogeneous group of tumors. The prognosis for patients with stage III NSCLC remains poor, and the 5-year survival rate is not more than 20 %. Therefore, an actual problem is to develop prognostic indicators that would allow predicting the progression of the tumor process in patients in order to correctly build strategy and tactics for their treatment.The objective of the study was to clarify and substantiate the possibility of using laboratory parameters characterizing the level of blood proteins – participants in carcinogenesis in predicting the NSCLC progression in patients with stage III disease.In 1187 patients who were first diagnosed with stage III NSCLC, the duration of the relapse-free period after treatment was analyzed using the observation results for one year. The mean age of patients was 63 ± 23 years. In 89 patients (58 ± 23.5 years), the concentration of CYFRA 21-1, SCC, TPA were determined by electrochemiluminescent method; pyruvate kinase M2, CXCL5, CXCL8 chemokines – by enzyme immunoassay; CXCR1 and CXCR2 receptors– by flow cytometry.A proportional hazards model was used to identify potentially informative indicators for predicting the duration of the relapse-free period in patients with stage III NSCLC: the levels of lymphocytes containing CXCR1 and CYFRA 21-1. Based on the one-year observation results and the graphical analysis of Kaplan-Meier, groups of low (T1N2M0, T3N1M0, T2N2M0, T4N0M0, T3N2M0) and high (T1N3M0, T2N3M0, T3N3M0, T4N1M0, T4N2M0, T4N3M0) risk of tumor progression were identified. High-risk patients had a higher level of CYFRA 21-1, a relative content of the receptor CXCR1 in lymphocytes, and a relative content of the receptor CXCR2 in monocytes compared to low-risk patients (p < 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %. The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.>< 0.05). With their participation, based on the results of logistic regression analysis, an equation was constructed, the calculation of which makes it possible to predict the risk of tumor recurrence. The threshold value of the equation is 0.519. The sensitivity of the prediction model was 80.9 %, the specificity was 83.3 %, and the prediction value of a positive result was 84.4 % and that of a negative result – 79.6 %.The study results give grounds to recommend a set of laboratory parameters in the blood of stage III NSCLC patients, including the CYFRA 21-1 level and the receptors CXCR1 and CXCR2, in order to assess their tumor progression risk.