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

摘要:

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χ²检验，差异有统计学意义（χ² =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。

Abstract:

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 group Ⅲ/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-γ and both combined to predict the prognostic value of NSCLC patients were analyzed.Results Serum NKG2D in stage Ⅲ/Ⅳ group [(67.12 ± 5.28)%] was lower than that in stage I/Ⅱ group [(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 stage Ⅲ/Ⅳ group were higher than those in stage Ⅲ/Ⅳ group [ (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-γ was 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 stage Ⅲ/Ⅳ group were 28.00% (28/100), while those in the stage I/Ⅱ group were 12.00% (6/50) within six months. The difference was statistically significant with χ² test (χ² = 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-γ are 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.