| Objective To explore the involvement of cytokines and inflammatory cells in the occurrence and development of lung cancer and their clinical significance,12 classes of cytokines and 3 classes of inflammatory cells were analyzed for changes in peripheral blood expression in lung cancer patients.Methods A total of 483 lung cancer patients and 44 healthy people diagnosed at the affiliated hospital of Qingdao University between March 2020 and October 2022 were selected,414 patients of non-small cell lung cancer(NSCLC)and 44 patients of small cell lung cancer(SCLC)were used to studying the expression changes of cytokines and inflammatory cells before antitumor therapy.87 newly diagnosed patients with advanced lung cancer(52 patients of NSCLC and 35 patients of SCLC)were used to observe the changes of cytokines and inflammatory cells in patients with different chemotherapy efficacy,according to the response evaluation criteria in solid tumors,the patients were divided into complete response(CR),partial response(PR),stable disease(SD)and progressive disease(PD).Interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,IL-12P70,IL-17,interferon(IFN)-α,IFN-γ,tumor necrosis factor(TNF)-α levels in peripheral blood were measured by multi-microsphere immunofluorescence assay,and absolute neutrophil count(ANC),absolute lymphocyte count(ALC)and absolute monocyte count(AMC)were measured by blood cell analyzer.Serum carcinoembryonic antigen(CEA),neuron-specific enolase(NSE),cytokeratin 19 fragment(CYFRA 21-1),carbohydrate antigen 125(CA 125),squamous cell carcinoma antigen(SCCA),and gastrin-releasing peptide precursors(Pro GRP)levels of six lung cancer-related tumor markers were detected by chemiluminescence method.Nonparametric rank-sum tests were used for group-wise comparison,and Spearman’s correlation tests were used to analyze the correlation between the two variables.The x~2test was used for the comparison of the positive rates.Results 1.There were statistical differences in IL-2,IL-5,IL-6,IL-8 and TNF-α levels in plasma among non-small cell lung cancer(NSCLC),small cell lung cancer(SCLC)and the control groups(H = 6.025,10.292,29.821,7.589 and 11.361,P < 0.05),there were no significant differences in the other seven cytokines levels between the three groups(P > 0.05).Compared with the control group,IL-5,IL-6,IL-8 and TNF-α levels in the NSCLC group were significantly increased(Z =-4.170,-2.500,-3.230 and-3.208,P < 0.05),while the IL-2 level decreased(Z = 2.436,P < 0.05).IL-6,IL-8 and TNF-α levels in the SCLC group were significantly increased(Z =-5.414,-2.538 and-2.884,P < 0.05),while IL-2 and IL-5 levels were not significantly changed(Z = 1.416 and-2.162,P > 0.05).IL-6 level was increased in the SCLC group compared to the NSCLC group(Z =-3.109,P < 0.01),while the plasma levels of IL-2,IL-5,IL-8 and TNF-α were not significantly changed(Z =-0.533,0.301,-0.912 and-0.648,P > 0.05).And in the NSCLC group,there was an increase in IL-2 and IL-6 levels in the lung squamous cell carcinoma group compared to the lung adenocarcinoma group(Z =-2.653 and-4.300,P < 0.01),while the levels of IL-5,IL-8 and TNF-α were not significantly different(Z =-0.277,-0.405 and-1.405,P > 0.05).2.The levels of ANC,ALC,AMC,NLR and MLR in peripheral blood were different among NSCLC,SCLC and the control groups(H = 21.725,22.653,21.885,43.562 and 62.339,P < 0.001).Compared to the control group,ANC,AMC,NLR and MLR levels in the NSCLC group were increased(Z =-4.411,-4.226,-5.616 and-6.361,P < 0.05),and the ALC level decreased(Z = 3.523,P < 0.05).ANC,AMC,NLR and MLR levels in the SCLC group were increased(Z =-4.081,-4.327,-6.342 and-7.739,P < 0.001),and ALC level decreased(Z = 4.738,P < 0.001).Compared with the NSCLC group,NLR and MLR levels in the SCLC group were significantly increased(Z =-2.911,-4.045,P < 0.05),and ALC level was significantly decreased(Z = 2.847,P < 0.05),there was no significant change in the levels of ANC and AMC(Z =-1.076,-1.592,P > 0.05).And in the NSCLC group,ANC,AMC,NLR and MLR levels were raised in the lung squamous cell carcinoma group compared to the lung adenocarcinoma group(Z =-4.933,-5.265,-4.397 and-5.508,P < 0.01),while there was no significant change in ALC level(Z =-0.608,P > 0.05).3.Compared with the healthy control group,the positive expression rate of cytokines with changes in NSCLC was the highest in TNF-α(66.4%),followed by IL-2(44.9%),IL-8(44.0%),IL-5(40.6%)and IL-6(36.7%).The positive expression rate of TNF-α in SCLC was the highest(68.2%),and the other indicators from high to low were IL-6(59.1%),IL-8(50.0%),IL-2(43.2%)and IL-5(27.3%).The positive expression rate of IL-6 in SCLC was significantly higher than that in NSCLC(x~2= 8.381,P = 0.004),and the positive expression rates of the other four cytokines were not significantly different(P > 0.05).MLR had the highest positive expression rate of inflammatory cells with changes in NSCLC(60.1%),followed by ANC(52.9%),AMC(47.6%),NLR(42.5%)and ALC(41.1%).MLR had the highest positive expression rate in SCLC(84.1%),the other indicators from high to low were NLR(65.9%),ALC(61.4%),ANC(59.1%)and AMC(56.8%).Meanwhile,the positive expression rates of ALC,NLR and MLR in SCLC were significantly higher than those in NSCLC(x~2= 6.687,8.806 and 9.725,P < 0.05).There was no significant difference in the positive expression rates of ANC and AMC between the two groups(x~2= 0.613,1.358,P > 0.05).4.The results of cytokine levels in different stages of lung cancer patients show that the IL-5,IL-6 and IL-8 levels in plasma in advanced NSCLC patients(III/IV stage,n = 124)were significantly higher than those in early NSCLC patients(I/II stage,n = 290)(Z =-2.72,-6.219 and-2.462,P < 0.05),while IL-2 and TNF-α levels were not significantly changed(Z =-1.716,-1.696,P > 0.05).In the advanced SCLC group(n = 32),the IL-6 level was significantly higher than that in the early stage(n = 12)(Z =-2.491,P < 0.05),while IL-2,IL-5,IL-8 and TNF-α levels were not significantly changed(Z =-1.601,-0.132,-0.330 and-0.542,P > 0.05).5.The expression of inflammatory cells in patients with different stages of lung cancer showed that the levels of ANC,AMC,NLR and MLR in the peripheral blood of patients in the advanced NSCLC group(III/IV stage,n = 124)were significantly higher than those in early stage(I/II stage,n = 290)(Z =-5.149,-3.238,-4.809 and-3.349,P < 0.05),while there was no significant change in ALC level(Z =-0.602,P > 0.05).In the advanced SCLC group(n = 32),the levels of peripheral blood NLR and MLR were higher than those in the early stage(n = 12)(Z =-2.688,-3.347,P < 0.05),while the levels of ALC were significantly decreased(Z =-2.531,P < 0.05),while the levels of ANC and AMC were not significantly changed(Z =-0.922,-1.529,P > 0.05).6.Correlation analysis between plasma cytokine levels and serum tumor markers in patients with lung cancer showed that plasma IL-6 levels were positively correlated with serum CEA,CA 125 and CYFRA 21-1 levels in patients with NSCLC and serum Pro GRP and NSE levels in SCLC patients(r = 0.183,0.178,0.424,0.389 and 0.303,P < 0.05).The plasma IL-8 level was positively correlated with the serum Pro GRP level in SCLC patients(r = 0.337,P < 0.05).There was no correlation between other cytokines and tumor markers.7.After 4 cycles of first-line chemical therapy for 87 patients with lung cancer,the levels of IL-6,IL-8 and TNF-α in the disease control group(CR + PR + SD)were lower than those before treatment(Z =-4.193,-2.078 and-3.204,P < 0.05),the levels of IL-6,IL-8 and TNF-α were increased in the disease progression group(PD)(Z =-2.166,-2.139 and-2.167,P < 0.05).Meanwhile,ANC,ALC and NLR in the disease control group were lower than those before treatment(Z =-5.216,-2.036 and-2.787,P < 0.05),there was no significant change in AMC and MLR levels(Z =-1.641,-0.025,P > 0.05).ANC,AMC,NLR and MLR were increased in the disease progression group(Z =-2.112,-2.400,-2.866 and-3.242,P < 0.05),but ALC level decreased(Z =-2.274,P < 0.05).And after 4 cycles of chemical therapy for patients with lung cancer,the levels of IL-6,IL-8 and TNF-α in the disease progression group were increased than those in the disease control group(Z =-3.128,-3.382 and-3.789,P < 0.05).ANC,AMC,NLR and MLR in the disease progression group were increased than those in the disease control group(Z =-4.976,-3.654,-4.868 and-3.944,P < 0.05),while ALC level decreased(Z =-2.087,P < 0.05).Meanwhile,after 4 cycles of treatment,the decrease of plasma IL-6,but not IL-8 and TNF-α in disease control group was higher than that in serum CEA,CA 125 and SCCA(P < 0.05).The increase of plasma IL-8,but not IL-6 and TNF-α was higher than that of serum CA 125 and CYFRA 21-1 in disease progression group(P < 0.05).Conclusion1.Plasma cytokines IL-2,IL-5,IL-6,IL-8,TNF-α and peripheral blood inflammatory cells ANC,ALC,AMC are involved in the occurrence and development of NSCLC and SCLC to varying degrees,and are differentially expressed in lung cancer patients with different types and TNM stages.2.The levels of plasma cytokines IL-6,IL-8,TNF-α and peripheral blood inflammatory cells ANC,ALC,AMC,NLR and MLR in patients with advanced lung cancer after chemotherapy vary with the outcome of therapeutic effect.3.The plasma IL-6 level was positively correlated with the serum CEA,CA 125,CYFRA 21-1,Pro GRP and NSE levels,and the plasma IL-8 level was only positively correlated with the serum Pro GRP level. |
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