关键词: 非小细胞肺癌, 中性粒细胞与淋巴细胞数比值, 血清淀粉样蛋白A, 预后, 凋亡

Abstract: Objective The aims of this study were to investigate the relationship between the pre-treatment neutrophils to lymphocytes ratio(NLR)and prognosis of patients with non small cell lung cancer(NSCLC),and to explain the relevant mechanism. Methods A total of 302 NSCLC patients who received radiotherapy in Harbin Medical University Cancer Hospital from January 2007 to December 2009 were collected as the modeling group,and 96 patients from January 2010 to June 2010 were collected as the validation group.The ROC curve in the modeling group was used to evaluate the predictive value of NLR for patient recurrence;the relationship between NLR and clinical indications and prognosis before treatment,and the factors affecting the prognosis of patients were analyzed.A nomogram model was established and verified in the validation group.Immunohistochemistry was used to detect serum amyloid A(SAA)and neutrophil expression in tumor tissues;ELISA was used to detect the plasma concentration of SAA in patients;RT-PCR and Western blotting were used to detect the expression of SAA in NSCLC cells;Flow cytometry was used to analyze the effect of SAA on neutrophil apoptosis and detect the expression of apoptosis protein. Results The ROC curve in the modeling group showed that NLR had a certain diagnostic value for the recurrence of NSCLC patients before treatment(AUC=0.679,P=0.013),and the best cutoff of NLR was 2.53;Grouped by high and low NLR,NLR was correlated withand ECOG,pathological stage and tumor grade;Patients in the low NLR group have longer overall survival and disease-free survival(P＜0.01).The AUC values of the overall survival nomogram model for the prediction of the 3 and 5 year survival rates in the modeling group were 0.723 and 0.625,respectively,and the AUC values for the prediction of the 3 and 5 year survival rates in the validation group were 0.749 and 0.705,respectively.Patients with high NLR had a high neutrophil infiltration and high expression of SAA in tumor tissues(P＜0.01);The concentration of SAA in patients' serum was significantly increased(P＜0.01),and SAA concentration was positively correlated with the number of neutrophils(P＜0.01);expression of SAA mRNA and protein in NSCLC cells were significantly increased(P＜0.01);Flow cytometry results showed that SAA effectively inhibited neutrophil apoptosis;After neutrophils treated with SAA,the expression of Caspase-3 decreased,and Bcl-2 expression increased(P＜0.05). Conclusion The level of NLR before treatment can be used as an indicator of prognostic risk for NSCLC patients;SAA inhibits neutrophil apoptosis and affects the level of NLR.

Key words: Non-small cell lung cancer;Neutrophils to lymphocytes ratio;Serum amyloid A;Prognosis;Apoptosis