血清HE4和IL-6对非小细胞肺癌的诊断价值研究

Diagnostic value of serum HE4 and IL-6 in non-small cell lung cancer

目的探讨人附睾蛋白4(HE4)和白细胞介素-6(IL-6)对非小细胞肺癌(NSCLC)的诊断价值。方法选取2020年1月—2022年12月在河北省人民医院住院治疗的50例NSCLC患者作为肺癌组,同期50例健康体检者作为对照组进行回顾性分析,采用电化学发光法检测血清HE4、IL-6水平,分析比较二组患者基本特征、HE4和IL-6水平差异,运用Logistic回归分析筛选出诊断NSCLC有效指标,构建诊断NSCLC的预测模型。并通过ROC曲线分析血清HE4、IL-6对NSCLC的诊断价值。结果肺癌组血清HE4水平[(198.12±66.42)pmol/L]高于对照组[(79.56±15.77)pmol/L],肺癌组血清IL-6水平[(16.45±8.96)pg/ml]高于对照组[(4.96±1.91)pg/ml],差异有统计学意义(P<0.05),二组在年龄、性别分布上差异均无统计学意义(P>0.05);分别对不同临床特征的血清HE4和IL-6表达水平进行比较得出结论,NSCLC患者的血清HE4和IL-6表达水平与年龄、性别、病理类型比较差异均无统计学意义(P>0.05);Ⅲ~Ⅳ患者血清HE4和IL-6水平高于Ⅰ~Ⅱ(t=-2.440,P<0.018;t=-2.889,P<0.006),无远处转移患者血清HE4和IL-6水平明显低于存在远处转移患者(t=2.455,P<0.018;t=2.040,P<0.047);设自变量X1=HE4,X2=IL-6,以病理诊断结果为因变量做二元Logistic回归分析,得出患肺癌的概率预测回归模型为Logit(P)=0.084X1+0.538X2-13.299,该模型预测准确率可达98.0%;血清HE4和IL-6水平均与NSCLC发生有密切关系;通过ROC曲线分析显示,血清HE4对NSCLC的诊断阈值为≥110.73pmol/L,曲线下面积(AUC)为0.948(95%CI:0.896~0.998)。使用110.73pmol/L的截止点,HE4的敏感度为90.0%,特异性为98.0%;血清IL-6对NSCLC的诊断阈值为≥7.16pg/ml,曲线下面积(AUC)为0.869(95%CI:0.784~0.954)。使用7.16pg/ml的截止点,IL-6的敏感度为84.0%,特异性为92.0%;血清HE4和IL-6联合检测对NSCLC的诊断的敏感度为98.0%,特异性为96.0%。结论血清HE4、IL-6对NSCLC的诊断具有一定的价值,通过HE4、IL-6血清肿瘤标志物建立的预测模型,对NSCLC的早期预测具有较好的价值。

Objective To investigate the diagnostic value of human epididymal protein 4(HE4)and Interleukin 6(IL-6)in non-small cell lung cancer(NSCLC).Methods Fifty NSCLC patients who were hospitalized at Hebei Provincial People's Hospital from January 2020 to December 2022 were selected as the lung cancer group,fifty healthy individuals in the same period as the control group retrospective analysis was performed.Serum HE4 and IL-6 levels were measured using electrochemical luminescence method,and the basic characteristics and differences in HE4 and IL-6 levels between the two groups were analyzed and compared.Logistic regression analysis was used to screen effective indicators for diagnosing NSCLC,and a predictive model for diagnosing NSCLC was constructed.The diagnostic value of serum HE4 and IL-6 in NSCLC was analyzed by Receiver operating characteristic.Results The serum HE4 level in the lung cancer group[(198.12±66.42)pmol/L]was higher than that in the control group[(79.56±15.77)pmol/L],and the serum IL-6 level in the lung cancer group[(16.45±8.96)pg/ml]was higher than that in the control group[(4.96±1.91)pg/ml],with a statistically significant difference(P<0.05).There was no statistically significant difference in age and gender distribution between the two groups(P>0.05).Comparing the expression levels of serum HE4 and IL-6 with different clinical characteristics,it was concluded that there was no statistically significant difference in expression levels of serum HE4 and IL-6 with age,gender,and pathological type in NSCLC patients(P>0.05).The serum HE4 and IL-6 levels in III-IV patients were higher than those in I-II(t=-2.440,P<0.018;t=-2.889,P<0.006),and serum HE4 and IL-6 levels in patients without distant metastasis were significantly lower than those in patients with distant metastasis(t=2.455,P<0.018;t=2.040,P<0.047),with a statistically significant difference.Assuming the independent variables X1=HE4 and X2=IL-6,a binary logistic regression analysis was performed with pathological diagnosis results as the dependent variable.The probability prediction regression model for lung cancer was obtained as Logit(P)=0.084X1+0.538X2-13.299,with a prediction accuracy of 98.0%.There is a close relationship between the average levels of serum HE4 and IL-6 water and the occurrence of NSCLC.Receiver operating characteristic analysis showed that diagnostic threshold of serum HE4 for NSCLC was≥110.73pmol/L,and the area under the curve(AUC)was 0.948(95%CI:0.896~0.998).Using a cut-off point of 110.73pmol/L,the sensitivity and specificity of HE4 were 90.0%and 98.0%,respectively.The diagnostic threshold of serum IL-6 for NSCLC is≥7.16pg/ml,and the area under the curve(AUC)is 0.869(95%CI:0.784~0.954).Using a cut-off point of 7.16pg/ml,the sensitivity and specificity of IL-6 were 84.0%and 92.0%,respectively.The sensitivity and specificity of the combined detection of serum HE4 and IL-6 in the diagnosis of NSCLC were 98.0%and 96.0%,respectively.Conclusion Serum HE4 and IL-6 have certain value in the diagnosis of NSCLC.The prediction model established through HE4 and IL-6 serum tumor markers has good value in early prediction of NSCLC.