抗菌肽hCAP18在非小细胞肺癌患者血清中的表达及其临床应用价值

Expression and clinical application value of antimicrobial peptide hCAP18 in serum of NSCLC patients

目的探讨非小细胞肺癌（NSCLC）患者血清抗菌肽人类阳离子抗菌蛋白18（hCAPl8）水平的变化及其在NSCLC辅助诊断和预后中的价值。方法采用病例对照研究。选择同济大学附属同济医院胸外科2011年1月至2012年1月NSCLC患者标本50例（其中腺癌28例，鳞癌22例）及同期体检科50名健康对照者进行研究，用酶联免疫吸附实验（ELISA）检测血清中hCAPl8的浓度，并比较NSCLC患者术前和术后血清中hCAPl8的浓度变化情况；通过分析受试者工作特征曲线（ROC）判断hCAPl8浓度在NSCLC诊断中敏感度和特异度。采用t检验和Log—rank检验等方法进行统计学分析。结果NSCLC患者血清中的hCAPl8浓度为（6733．0±771．8）μg／L，明显高于健康对照组的（253．0±6．9）μg／L，差异有统计学意义（t=8．396，P〈0．05）；hCAP18在肺鳞癌和腺癌患者血清中浓度分别为（6300．0±1221．0）μg／L和（7074．0±1005．0）μg／L，差异无统计学意义（t=0．4942，P〈0．05）；在NSCLC患者肿瘤切除后30d血清hCAPl8的浓度为（433．6±38．2）μg／L，明显低于术前的（6733．0±771．8）μg／L，差异有统计学意义（t=8．512，P〈0．05）。血清hCAPl8检测NSCLC的ROC曲线下面积为0．931（95％CI=0．884～0．978），对NSCLC诊断的敏感度和特异度分别达到95．0％和96．3％，优于肺癌肿瘤标志物细胞角蛋白19（CYFRA21．1）[0．873（95％CI=0．758～0．917）]对NSCLC的辅助诊断效能。血清hCAP18〈390．0μg／L的NSCLC患者的复发率为12．5％（4／32），而血清hCAP18〉390．0μg／L的NSCLC患者的复发率为44．4％（8／18），差异有统计学意义（x2=22．64，P〈0．05）。结论血清hCAP18检测对NSCLC的辅助诊断具有良好的敏感度和特异度，有可能成为一项潜在的检测指标应用于肺癌的无创诊断和病情监测。

Objective To evaluate the serum level of antimicrobial peptide human cationic antimicrobial protein 18 （hCAP18） in non-small cell lung cancer （NSCLC） patients and its auxiliary diagnosis and prognosis value. Methods Case-control study was used. The serum level of hCAP18 was measured by enzyme linked immunosorbent assay （ELISA） in 50 cases with NSCLC patients of department of thoracic surgery and 50 cases healthy people of department of physical examination from January 2011 to January 2012 in Tongji Hospital of Tongji University. The concentrations of hCAP18 in serum of NSCLC patients before and after surgery were analyzed. The sensitivity and specificity of serum hCAP18 for the diagnosis of NSCLC were evaluated using the receiver operating characteristic （ROC） curves. Data was analyzed by using the t-test and Log-rank test. Results Serum hCAP18 concentration in NSCLC patients （6 733 ±771.8 ） μg/L was significantly higher than in healthy controls （253± 6. 9） μg/L（t = 8. 396, P 〈 0. 05）. However, the concentration of hCAP18 showed no significant difference between squamous cell carcinoma and adenocareinoma[ （6 300. 0 ± 1 221.0） μg/L and （7 074. 0 ± 1 005.0） μg/L, respectively; t=0.494 2, P 〈 0.05]. hCAP18 levels had significantly decreased in serum of NSCLC patients after 30 d surgery compared to preoperative results[from （6 733.0 ±771.8） μg/L to （433.6 ±38.2） Ixg/L; t = 8.512, P 〈 0. 05 ]. ROC analysis of serum hCAP18 yielded an AUC （ Area under the ROC curve） of 0. 931 （95% CI = 0. 884- 0.978） with 95% sensitivity and 96. 3% specificity, which was higher than the CYFRA21-1 [ 0. 873 （95% CI = 0. 758 - 0. 917） ]. The relapse rate of NSCLC patients with serum hCAP18 ≤390. 0 μg/L was 12.5% （4/32）, while 44. 4% （8/18） in NSCLC patients with serum hCAP18 〉390. 0 μg/L （X2 = 22. 64, P 〈 0. 05 ）. Conclusions Detection of serum hCAP18 shows a good sensitivity and specificity for the auxiliary diagnosis of NSCLC. It is possible to be a potential detection index for noninvasive diagnosis and monitoring progression of lung cancer.