Development of a Protein Biomarker Panel to Detect Non-Small-Cell Lung Cancer in Korea

Clin Lung Cancer. 2017 Mar;18(2):e99-e107. doi: 10.1016/j.cllc.2016.09.012. Epub 2016 Oct 5.


Background: Lung cancer screening using low-dose computed tomography reduces lung cancer mortality. However, the high false-positive rate, cost, and potential harms highlight the need for complementary biomarkers. We compared the diagnostic performance of modified aptamer-based protein biomarkers with Cyfra 21-1.

Patients and methods: Participants included 100 patients diagnosed with lung cancer, and 100 control subjects from Asan Medical Center (Seoul, Korea). We investigated candidate biomarkers with new modified aptamer-based proteomic technology and developed a 7-protein panel that discriminates lung cancer from controls. A naive Bayesian classifier was trained using sera from 75 lung cancers and 75 controls. An independent set of 25 cases and 25 controls was used to verify performance of this classifier. The panel results were compared with Cyfra 21-1 to evaluate the diagnostic accuracy for lung nodules detected by computed tomography.

Results: We derived a 7-protein biomarker classifier from the initial train set comprising: EGFR1, MMP7, CA6, KIT, CRP, C9, and SERPINA3. This classifier distinguished lung cancer cases from controls with an area under the curve (AUC) of 0.82 in the train set and an AUC of 0.77 in the verification set. The 7-marker naive Bayesian classifier resulted in 91.7% specificity with 75.0% sensitivity for the subset of individuals with lung nodules. The AUC of the classifier for lung nodules was 0.88, whereas Cyfra 21-1 had an AUC of 0.72.

Conclusion: We have developed a protein biomarker panel to identify lung cancers from controls with a high accuracy. This integrated noninvasive approach to the evaluation of lung nodules deserves further prospective validation among larger cohorts of patients with lung nodules in screening strategy.

Keywords: Aptamer; Biomarker; Cyfra 21-1; Lung cancer screening; Lung nodule.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / diagnosis*
  • Antigens, Neoplasm / blood
  • Aptamers, Peptide / metabolism
  • Area Under Curve
  • Bayes Theorem
  • Biomarkers, Tumor / blood*
  • Carcinoma, Large Cell / blood
  • Carcinoma, Large Cell / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / diagnosis*
  • Case-Control Studies
  • Early Detection of Cancer
  • Female
  • Humans
  • Keratin-19 / blood
  • Lung Neoplasms / blood
  • Lung Neoplasms / diagnosis*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proteomics / methods*


  • Antigens, Neoplasm
  • Aptamers, Peptide
  • Biomarkers, Tumor
  • Keratin-19
  • antigen CYFRA21.1