血清NK细胞活化性受体、γ干扰素与非小细胞肺癌患者病情程度、预后的相关性分析

Correlation analysis of serum NKG2D and IFN-γ levels with disease severity and prognosis of patients with non-small cell lung cancer

目的分析血清NK细胞活化性受体(NKG2D)、γ干扰素(IFN-γ)与非小细胞肺癌(NSCLC)患者病情程度、预后的相关性。方法选取沧州市中心医院2020年5月—2021年5月收治的NSCLC患者150例为研究对象,根据TNM分期标准分为Ⅰ、Ⅱ期组50例和Ⅲ、Ⅳ期组100例。比较两组患者的血清NKG2D、IFN-γ、肿瘤标志物[癌胚抗原(CEA)、细胞角质蛋白19片段抗原21-1(CYFRA21-1)、糖类抗原125(CA125)]及6个月内病死率;采用Pearson法检验血清NKG2D、IFN-γ与肿瘤标志物的相关性;比较不同预后NSCLC患者血清NKG2D、IFN-γ;绘制ROC曲线,分析血清NKG2D、IFN-γ及两者联合预测NSCLC患者预后的价值。结果Ⅲ、Ⅳ期组血清NKG2D[(67.12±5.28)%]低于Ⅰ、Ⅱ期组[(81.50±7.33)%](P<0.05),血清IFN-γ[(23.67±5.74)ng/mL]、CEA[(43.76±6.48)ng/mL]、CA125[(35.62±6.03)u/mL]、CYFRA21-1[(11.69±1.86)ng/mL]高于Ⅰ、Ⅱ期组[(17.91±4.82)ng/mL、(21.53±4.62)ng/mL、(23.59±5.17)u/mL、(6.84±1.12)ng/mL](P<0.05)。Pearson相关性分析显示,血清NKG2D与CEA(r=-0.683)、CA125(r=-0.615)、CYFRA21-1(r=-0.704)均呈负相关(P<0.05);IFN-γ与CEA(r=0.512)、CA125(r=0.439)、CYFRA21-1(r=0.543)均呈正相关(P<0.05)。150例NSCLC患者病死率为22.67%(34/150)。Ⅲ、Ⅳ期组6个月内病死率为28.00%(28/100),Ⅰ、Ⅱ期组6个月内病死率为12.00%(6/50),经χ^(2)检验,差异有统计学意义(χ^(2)=4.868,P=0.027)。死亡组血清NKG2D[(58.58±5.62)%]低于非死亡组[(84.23±4.39)%](P<0.05),血清IFN-γ[(29.93±3.17)ng/mL]高于非死亡组[(20.95±2.20)ng/mL](P<0.05)。ROC曲线显示,IFN-γ、NKG2D及两者联合预测NSCLC患者预后的AUC分别为0.780(95%CI:0.673,0.942)、0.820(95%CI:0.675,0.955)、0.860(95%CI:0.761,0.984),敏感性分别为78.1%(95%CI:0.648,0.892)、82.6%(95%CI:0.713,0.955)、86.5%(95%CI:0.752,0.978),特异性为51.3%(95%CI:0.443,0.714)、53.6%(95%CI:0.467,0.735)、41.5%(95%CI:0.328,0.616)。结论血清NKG2D、IFN-γ与NSCLC患者病情程度、肿瘤标志物水平有关,且两者联合检测可有效预测患者早期预后。

Objective To analyze the correlation of serum NK cell activation receptor(NKG2D)and IFN-γ(IFN-γ)levels with the severity and prognosis of non-small cell lung carcinoma(NSCLC)patients.Methods A total of 150 NSCLC patients admitted to Cangzhou Central Hospital from May 2020 to May 2021 were selected as research subjects and divided into group Ⅰ/Ⅱ(50 cases)and groupⅢ/Ⅳ(100 cases)according to TNM staging criteria.The two groups of serum NKG2D,IFN-γ,tumor markers[carcinoembryonic antigen(CEA),human cytokeratin 21-1 fragment(CYFRA21-1),sugar antigen 125(CA125)],and 6-month survival rate were recorded.Bivariate Pearson linear correlation was used to test serum NKG2D,IFN-γ,and tumor markers.the serum levels of NKG2D and IFN in different prognosis NSCLC patients were compared to draw the ROC curve,and the value of serum NKG2D,IFN-γand both combined to predict the prognostic value of NSCLC patients were analyzed.Results Serum NKG2D in stageⅢ/Ⅳgroup[(67.12±5.28)%]was lower than that in stage Ⅰ/Ⅱgroup[(81.50±7.33)%](P<0.05).Serum IFN-γ[(23.67±5.74)ng/mL],CEA[(43.76±6.48)ng/mL],CA125[(35.62±6.03)u/mL],CYFRA21-1[(11.69±1.86)ng/mL]in stageⅢ/Ⅳgroup were higher than those in stageⅢ/Ⅳgroup[(17.91±4.82)ng/mL,(21.53±4.62)ng/mL,(23.59±5.17)u/mL,(6.84±1.12)ng/mL](P<0.05);Pearson correlation analysis showed that serum NKG2D was negatively correlated with CEA level(r=−0.683),CA125 level(r=−0.615),and CYFRA21-1 level(r=−0.704)(P<0.05).IFN-γwas positively correlated with CEA level(r=0.512),CA125 level(r=0.439),and CYFRA21-1 level(r=0.543)(P<0.05).The overall mortality rate in 150 patients with NSCLC was 22.67%(34/150).The mortality rates within six months in the stageⅢ/Ⅳgroup were 28.00%(28/100),while those in the stage Ⅰ/Ⅱgroup were 12.00%(6/50)within six months.The difference was statistically significant with χ^(2) test(χ^(2)=4.868,P=0.027).Serum NKG2D[(58.58±5.62)%in the death group was lower than that in the non-death group[(84.23±4.39)%],and serum IFN-γ[(29.93±3.17)ng/mL]was higher than that in the non-death group[(20.95±2.20)ng/mL](P<0.05).The ROC curve results showed that the AUC of IFN-γ,NKG2D,and both combined outcome prediction outcomes was 0.780(95%CI:0.673,0.942),0.820(95%CI:0.675,0.955),and 0.860(95%CI:0.761,0.984)in NSCLC patients,respectively;the sensitivity were 78.1%(95%CI:0.648,0.892),82.6%(95%CI:0.713,0.955),86.5%(95%CI:0.752,0.978);the specificity were 51.3%(95%CI:0.443,0.714),53.6%(95%CI:0.467,0.735),41.5%(95%CI:0.328,0.616).Conclusion The levels of serum NKG2D and IFN-γare related to the severity of NSCLC and the levels of tumor markers,and the combination of the two can effectively predict the early prognosis of NSCLC.