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H. Zhang



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    P3.06 - Poster Session/ Screening and Early Detection (ID 220)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Screening and Early Detection
    • Presentations: 1
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      P3.06-007 - Discovery and Validation of Potential Glycoprotein Biomarkers in the Airway Fluid to Improve the Detection of Lung Cancer from Benign Lung Nodule (ID 925)

      09:30 - 09:30  |  Author(s): H. Zhang

      • Abstract

      Background:
      Recent clinical screening trials using highly sensitive low-dose computed tomography (LDCT) demonstrated an increased detection proportion of stage I lung cancers and improved overall survival of lung cancer patients as the result of early detection. However, lung cancer screening trials also showed high repeat screening rates and false-positive rates causing unnecessary second-line invasive procedures and surgery. New strategies are still needed to improve the specificity of lung cancer screening. The airway fluid, bronchoalveolar lavage (BAL), is commonly used for the evaluation of lung nodules and diagnosis of lung cancers. Proteins in the BAL fluid may serve as potential biomarkers for cancer detection. In this study, we examined the protein profile, particularly the signature of glycoprotein in normal and lung cancer patients.

      Methods:
      We collected BAL fluid after cellular components were harvested for cytological examination in the cytology laboratory. Protein profile and N-glycoproteins were analyzed using the solid-phase extraction of N-glycoprotein (SPEG) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixteen BAL samples, including four cases each of benign lung disease, adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and small cell carcinoma (SCLC), were analyzed.

      Results:
      A total of 1013 unique peptides from 457 glycoproteins were identified and quatified. Among them, 286 proteins were identified in BAL of ADC, 363 in squamous cell carcinoma (SqCC), 298 in SCLC and 330 in benign BALs. In addition to common proteins found in all groups, we identified 113 unique proteins that were differentially expresssed in benign disease, ADC, SqCC and SCLC, respectively. The levels of Napsin A, periostin, Galectin-3-binding protein (G3-BP) and myeloperoxidase (MPO) in cancer and benign BALs were further validated using independently collected BAL specimens by ELISA assays (Table 1). Table1. Detection of Proteins in BAL from lung cancer and benign lung disease by ELISA assays.

      Protein Benign* (n=7) ADC* (n=18) SqCC* (n=9) SCLC* (n=6) Sensitivity (%) Specificity (%) PPV (%) NPV (%) P value
      Napsin A 55±39 295±104 102±34 50±28 83.3 66.7 88.2 57.1 <0.05
      Periostin 255±104 4002±218 3496±1765 1772±1119 73.68 71.43 87.5 50.0 <0.05
      G3-BP 168±29 290±70 240±65 132±65 47.4 11.8% 69.2 23.1 >0.05
      MPO 3227±2948 0.08±0.03 1.6±0.7 0.1±0.06 33.3 100 100 83.3 <0.05**
      * protein concentration was expressed as ng/mg total BAL protein. ** for benign lesions.

      Conclusion:
      Our study demonstrates that potential protein biomarkers in BAL fluid can be identified and quantified. They have the potential to improve the specificity of lung screening tests and to reduce unnecessary surgery in patients with benign lung nodules.