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A. Nogal



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    MO11 - Screening and Epidemiology (ID 131)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Imaging, Staging & Screening
    • Presentations: 1
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      MO11.11 - IL-11 and CCL-1: Novel protein diagnostic biomarkers of lung adenocarcinoma in bronchoalveolar lavage (BAL) (ID 2876)

      17:15 - 17:20  |  Author(s): A. Nogal

      • Abstract
      • Presentation
      • Slides

      Background
      Lung cancer (LC) and chronic obstructive pulmonary disease (COPD) are smoking related diseases and the presence of COPD increases itself the risk of developing lung cancer, probably due to underlying inflammation. LC is typically detected at late stages of the disease and carries a dismal prognosis. There is an unmet need for useful early detection methods of lung cancer in high risk subjects, such as smokers.

      Methods
      The expression of inflammatory proteins was studied in bronchoalveolar lavage samples (BAL) by antibody arrays in a prospective discovery cohort of 60 patients with the following inclusion criteria: age > 40 years, diagnostic broncoscopy due to hemoptysis or pulmonary nodule, smokers or ex-smokers pack of more than 30 pack-years, divided into four groups (control, LC, COPD, LC & COPD). Relevant biomarkers were validated by western blot. Additional validation was carried out by ELISA in two independent controlled cohorts of 139 (control, LC, COPD, LC & COPD) and 160 patients (control, all LC histological subtypes).

      Results
      CCL-1 and IL-11 were selectively expressed in samples of adenocarcinoma patients, with or without COPD (p<0•001) in the discovery cohort. These proteins exhibited a remarkable diagnostic performance for lung adenocarcinoma in an independent cohort of 139 patients. ROC curves showed that the optimum diagnostic cutoff value for IL-11 was 42 pg/mL (area under curve [AUC] 0•93 [95% CI 0•896-0•975], sensitivity 90%, specificity 86%), and for CCL-1 was 39•5 pg/ml (0•83 [95% CI 0•749-0•902], sensitivity 83%, specificity 74%). Further validation of the ELISA biomarkers at the mentioned cutoffs was performed in an additional cohort of 160 patients (20 controls, 66 LC, 74 LC & COPD). There was a significant correlation between BAL levels of IL-11 and CCL-1 (r2= 0•76, p<0•001), and the use of both biomarkers increased the diagnostic accuracy to 96,1% in the two validation cohorts. Appropriate diagnostic performance was observed for all subgroups regardless of stage at diagnosis, involvement of bronchial tract, pack-years smoked, and number of cells in BAL.

      Diagnostic performance of IL-11 and CCL-1 in the first validation cohort (N=139)
      Adenocarcinoma vs all patients AUC (95%IC) Sensivity (95%IC) Specificity (95%IC) PPV (95%IC) NPV (95%IC) Positive LR Negative LR
      IL-11 0.93 (0.896-0.975) 90.2% (79%-95.7%) 88.7% (80.6%-93.5%) 80.7% (68.7%-88.9%) 94.5% (87.8%-97.6%) 7.95 (4.53-13.98) 0.11 (0.05-0.26)
      CCL-1 0.83 (0.749-0.902) 80% (66.4%-87.7%) 74.1% (63.9%-82.2%) 72.1% (59.2%-73.4%) 86.3% (76.6%-92.4%) 3.02 (2.05-4.47) 0.29 (0.17-0.52)
      IL11 and CCL-1 71.2% (57.7%-81.7%) 94.4% (88.4%-97.4%) 86% (72.7%-93.4%) 87.2% (79.9%-92.1%) 12.8 (5.77-28.41) 0.31 (0.20-0.47)
      IL-11 and/or CCL-1 94.3% (84.6%-98.1%) 74.1% (65.1%-81.4%) 64.1% (53%-73.9%) 96.4% (89.9%-98.8%) 3.64 (2.63-5.04) 0.08 (0.03-0.23)
      Diagnostic performance of IL-11 and CCL-1 in the second validation cohort (N=160)
      Adenocarcinoma vs all patients AUC (95%IC) Sensivity (95%IC) Specificity (95%IC) PPV (95%IC) NPV (95%IC) Positive LR Negative LR
      IL-11 0.95 (0.92-0.98) 90.6% (79.7%-95.9%9 83% (86.8%-87.7%) 60.8% (49.7%-70.8%) 96.8% (92.7%-98.6%) 5.32 (3.81-7.41) 0.11 (0.05-0.26)
      CCL-1 0.91 (0.87-0.96) 91.7% (80.4%-96.7%) 77.5% (71.0%-82.9%) 51.2% (40.8%-61.4%) 97.3% (93.3%-99%) 4.08 (3.09-5.04) 0.11 (0.04-0.28)
      IL11 and CCL-1 71.2% (57.7%-81.7%) 96.3% (92.5%-98.2%) 84.1% (70.6%-92.1%) 92.3% (87.7%-95.3%) 19.1 (9-41.13) 0.3 (0.19-0.46)
      IL-11 and/or CCL-1 92.3% 82.6%-98.1%) 84% (78%-88.5%) 62.5% (51.5%-72.3%) 98.1% (94.6%-99.4%) 5.88 (4.21-8.22) 0.07 (0.02-0.20)

      Conclusion
      IL-11 and CCL-1 are highly specific biomarkers with great accuracy for the diagnosis of lung adenocarcinoma in BAL specimens. Further study of these proteins as markers for early diagnosis and screening in plasma and other biological materials is warranted.

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