血清和胸腔积液HE4、CD147、SCC-Ag、CEA在诊断非小细胞肺癌合并恶性胸腔积液中的价值

Potential of a combination measurement of serum and pleural fluid levels of HE4,CD147,SCC-Ag and CEA in non-small cell lung cancer combined with malignant pleural effusion

目的探讨血清和胸腔积液中人附睾蛋白4(HE4)、细胞外基质金属蛋白酶诱导因子(CD147)、鳞状上皮细胞癌抗原(SCC-Ag)、癌胚抗原(CEA)对应的指标联合,在诊断非小细胞肺癌(NSCLC)合并恶性胸腔积液方面的价值。方法本研究为病例对照研究。采用非随机抽样的方法纳入2019年6月至2022年6月湖北民族大学附属民大医院的150例NSCLC合并恶性胸腔积液患者(恶性组)和50例良性胸腔积液患者(良性组)。比较2组血清和胸腔积液中HE4、CD147、SCC-Ag、CEA水平。采用受试者工作特征(ROC)曲线分析血清和胸腔积液中HE4、CD147、SCC-Ag、CEA对NSCLC患者合并恶性胸腔积液的诊断价值。采用Kappa检验比较病理诊断与血清和胸腔积液中HE4、CD147、SCC-Ag、CEA联合诊断NSCLC合并恶性胸腔积液的一致性,以任一指标阳性为联合诊断阳性。结果恶性组男80例,女70例,年龄(69.24±8.67)岁,吸烟70例。良性组男34例,女16例,年龄(68.54±8.34)岁,吸烟18例。2组患者性别、年龄、吸烟情况比较差异均无统计学意义(均P>0.05)。恶性组血清和胸腔积液中HE4、CD147、SCC-Ag、CEA水平均较良性组高(均P<0.001)。ROC曲线分析显示,血清HE4、CD147、SCC-Ag、CEA诊断NSCLC合并恶性胸腔积液的曲线下面积分别为0.821、0.856、0.923、0.943,胸腔积液中HE4、CD147、SCC-Ag、CEA诊断NSCLC合并恶性胸腔积液的曲线下面积分别为0.926、0.861、0.916、0.924。各指标诊断NSCLC合并恶性胸腔积液的最佳截断值分别为血清HE4141.89 pmol/L(敏感度0.687,特异度0.840)、血清CD14711.31μg/L(敏感度0.673,特异度0.920)、血清SCC-Ag 4.85μg/L(敏感度0.800,特异度0.920)、血清CEA 13.72μg/L(敏感度0.807,特异度0.940);胸腔积液HE41596.64 pmol/L(敏感度0.820,特异度0.860)、胸腔积液CD14716.13μg/L(敏感度0.807,特异度0.780)、胸腔积液SCC-Ag 21.76μg/L(敏感度0.840,特异度0.900)、胸腔积液CEA 26.15μg/L(敏感度0.847,特异度0.900)(均P<0.001)。一致性分析显示,2种检查方式具有较强的一致性,血清和胸腔积液中HE4、CD147、SCC-Ag、CEA联合检测的敏感度和特异度均高于血清或胸腔积液中单独指标检测(血清HE4+胸腔积液HE4:敏感度0.867,特异度0.880,Kappa=0.683;血清CD147+胸腔积液CD147:敏感度0.847,特异度0.920,Kappa=0.680;血清SCC-Ag+胸腔积液SCC-Ag:敏感度0.920,特异度0.940,Kappa=0.811;血清CEA+胸腔积液CEA:敏感度0.933,特异度0.960,Kappa=0.848)。结论血清和胸腔积液中HE4、CD147、SCC-Ag、CEA对应指标的联合检测对NSCLC合并恶性胸腔积液的诊断准确率、敏感度和特异度高。

ObjectiveTo explore the diagnostic potential of a combination measurement of serum and pleural fluid levels of human epididymis protein 4(HE4),extracellular matrix metalloproteinase inducer(CD147),squamous cell carcinoma antigen(SCC-Ag),and carcinoembryonic antigen(CEA)in non-small cell lung cancer(NSCLC)combined with malignant pleural effusion.MethodsThis was a case-control study.A total of 150 NSCLC patients combined with malignant pleural effusion(malignant group)and 50 patients with benign pleural effusion(benign group)who were admitted in Minda Hospital of Hubei Minzu University from June 2019 to June 2022 were enrolled using the non-random sampling.HE4,CD147,SCC-Ag and CEA levels in serum and pleural fluid were compared between the two groups.The diagnostic value of serum and pleural fluid levels of HE4,CD147,SCC-Ag and CEA in NSCLC combined with malignant pleural effusion was tested by the receiver operator characteristic(ROC)curves.Kappa test was used to compare the consistency between the combination measurement of serum and pleural fluid levels of HE4,CD147,SCC-Ag and CEA with the pathological diagnosis of NSCLC with malignant pleural effusion,and the positivity of any indicator was regarded as a positive combined diagnosis.ResultsThere were 80 males and 70 females in the malignant group,with the mean age of 69.24±8.67 years.There were 34 males and 16 females in the benign group,with the mean age of 68.54±8.34 years.There were no significant differences in gender,age,and smoking status between the two groups(all P>0.05).HE4,CD147,SCC-Ag,and CEA levels in the serum and pleural fluid of the malignant group were significantly higher than those of the benign group(all P<0.001).ROC analysis showed that the areas under curve(AUC)of serum HE4,CD147,SCC-Ag,CEA in diagnosing NSCLC with malignant pleural effusion were 0.821,0.856,0.923,0.943,respectively,and AUC of pleural fluid HE4,CD147,SCC-Ag,CEA were 0.926,0.861,0.916,0.924,respectively.The optimal cutoff values for diagnosing NSCLC with malignant pleural effusion were serum HE4 of 141.89 pmol/L(sensitivity=0.687,specificity=0.840)and serum CD147 of 11.31μg/L(sensitivity=0.673,specificity=0.920),serum SCC-Ag of 4.85μg/L(sensitivity=0.800,specificity=0.920),serum CEA of 13.72μg/L(sensitivity=0.807,specificity=0.940),pleural fluid HE4 of 1596.64 pmol/L(sensitivity=0.820,specificity=0.860),pleural fluid CD147 of 16.13μg/L(sensitivity=0.807,specificity=0.780),pleural fluid SCC-Ag of 21.76μg/L(sensitivity=0.840,specificity=0.900),and pleural fluid CEA of 26.15μg/L(sensitivity=0.847,specificity=0.900)(all P<0.001).Kappa test showed that the two diagnostic methods had a strong consistency.The sensitivity and specificity of the combined detection of HE4,CD147,SCC-Ag,and CEA in serum and pleural fluid were higher than those of the single detection(serum HE4+pleural fluid HE4:sensitivity=0.867,specificity=0.880,Kappa=0.683;serum CD147+pleural fluid CD147:sensitivity=0.847,specificity=0.920,Kappa=0.680;serum SCC-Ag+pleural SCC-Ag:sensitivity=0.920,specificity=0.940,Kappa=0.811;serum CEA+pleural fluid CEA:sensitivity=0.933,specificity=0.960,Kappa=0.848).ConclusionsA combination measurement of HE4,CD147,SCC-Ag,and CEA corresponding indicators in serum and pleural fluid has high diagnostic accuracy,sensitivity,and specificity for diagnosing NSCLC complicated with malignant pleural effusion.