KL-6在非小细胞肺癌术后辅助治疗性肺损伤中的诊断价值

Application Value of Serum Kreb Von Den Lungen-6 in the Adjuvant Treatment of Lung Injury after Non-small Cell Lung Cancer Surgery

  • 摘要:
      目的  探讨血清涎液化糖链抗原-6(kreb von den lungen-6,KL-6)在非小细胞肺癌(non-small cell lung cancer,NSCLC)术后辅助治疗性肺损伤中的诊断价值。
      方法  回顾性收集2017年11月—2020年7月中国医科大学附属盛京医院诊治的NSCLC患者(包括术后采用辅助治疗者和仅手术者)资料,以药物诱导性肺损伤(drug induced lung injury, DILI)、放射性肺损伤(radiation induced lung injury, RILI)诊断共识为判断NSCLC术后辅助治疗性肺损伤的诊断标准,将NSCLC术后辅助治疗患者分为肺损伤组和无肺损伤组,仅手术者为NSCLC手术组;以年龄和性别匹配同期体检中心的健康成人为健康对照组。肺损伤组于肺损伤确诊当日,无肺损伤组于辅助治疗的第3~4个月,NSCLC手术组分别于术前、术后7~10 d,健康对照组于体检当日,空腹采集静脉血检测血清KL-6。比较各组血清KL-6差异,并以无肺损伤组为对照,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估血清KL-6诊断NSCLC术后辅助治疗性肺损伤的效能。
      结果  共206例符合纳入和排除标准的患者入选本研究,其中肺损伤组51例,无肺损伤组52例,NSCLC手术组103例;健康对照组103例,基线资料均衡可比。血清KL-6水平由高至低依次为肺损伤组512.40(322.30,819.20)kU/L、NSCLC手术组(术前) 204.40(162.70,283.20)kU/L、健康对照组177.70(154.20,206.40)kU/L、无肺损伤组147.80(114.25,229.80)kU/L和NSCLC手术组(术后) 143.80(111.90,247.80)kU/L。除无肺损伤组与NSCLC手术组术后血清KL-6无统计学差异(P=0.879)外,其余两两比较差异均有统计学意义(P均<0.05)。ROC曲线分析显示,血清KL-6诊断NSCLC术后辅助治疗性肺损伤的曲线下面积(area under the curve,AUC)为0.972(95%CI:0.948~0.997),灵敏度、特异度、阳性似然比、阴性似然比分别为86.3%(95% CI:73.0%~94.1%)、96.2%(95% CI:86.2%~98.7%)、22.43(95% CI:5.74~87.69)、0.14(95% CI:0.07~0.28),最佳诊断临界值为310.15 kU/L。
      结论  NSCLC术后辅助治疗性肺损伤患者血清KL-6显著升高,其在NSCLC术后辅助治疗性肺损伤中具有较高的诊断价值,但仍需大样本前瞻性研究进一步验证。

     

    Abstract:
      Objective  To investigate the diagnostic value of serum kreb von den lungen-6 (KL-6) in lung injury from postoperative adjuvant treatment in non-small cell lung cancer (NSCLC).
      Methods  This study is a retrospective analysis including NSCLC with postoperative adjuvant treatment and NSCLC with merely surgical treatment patients diagnosed and treated in Shengjing Hospital of China Medical University from November 2017 to July 2020. Consensus on the diagnosis of drug induced lung injury and radiation induced lung injury was used as the diagnostic criteria for lung injury from postoperative adjuvant treatment. NSCLC patients with postoperative adjuvant treatment were divided into the lung-injury group and the non lung-injury group. those only with surgery were as NSCLC-surgery group. Match the healthy adults of the physical examination center at the same period as the healthy control group based on the age and gender. Fasting venous blood was collected from NSCLC patients and healthy adults for detection of serum KL-6. The time of venous blood collection was on the day of lung-injury diagnosis for the lung-injury group, after 3 to 4 months of adjuvant treatment for the non lung-injury group, before and 7 to 10 days after surgery for NSCLC-surgery group, and on the day of physical examination for the healthy control group. The levels of serum KL-6 in each group were compared, and the non lung-injury group was used as the control, the diagnostic threshold value of serum KL-6 for adjuvant therapeutic lung injury was preliminarily established based on the receiver operating characteristic(ROC) curve.
      Results  A total of 206 NSCLC patients who met the selection and exclusion criteria were enrolled, of which 51 cases were in lung-injury group, 52 cases were in non lung-injury group, and 103 cases were in NSCLC-surgery group. Meanwhile, 103 cases in healthy control group were enrolled. There was no significant difference among the basic clinical data of the four groups. The levels of serum KL-6 in the descending order were lung-injury group 512.40 (322.30, 819.20)kU/L, pre-operation of the NSCLC-surgery group 204.40 (162.70, 283.20)kU/L, healthy control group 177.70 (154.20, 206.40)kU/L, non lung-injury group 147.80 (114.25, 229.80)kU/L, and post-operation of the NSCLC-surgery group 143.80 (111.90, 247.80)kU/L. There was no significant difference in serum KL-6 between the non lung-injury group and post-operation of the NSCLC-surgery group (P=0.879), while the difference between other groups were statistically significant (all P < 0.05). The ROC curve analysis showed that the area under the curve (AUC) of serum KL-6 for the diagnosis of lung injury from NSCLC postoperative adjuvant treatment was 0.972 (95% CI: 0.948-0.997), and the diagnostic sensitivity, specificity, the positive and negative likelihood ratio were 86.3% (95% CI: 73.0%-94.1%), 96.2% (95% CI: 86.2%-98.7%), 22.43 (95% CI: 5.74-87.69), 0.14 (95% CI: 0.07-0.28), respectively. The best diagnostic cut-off value was 310.15 kU/L.
      Conclusions  Serum KL-6 is significantly increased in the patients with lung injury from NSCLC postoperative adjuvant treatment, and it has high application value in the diagnosis of lung injury from postoperative adjuvant treatment in NSCLC, but it still needs further verification by prospective studies with large samples.

     

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