Author of

• 12759

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  P3.17 - Poster Session 3 - Bronchoscopy, Endoscopy (ID 185)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12768

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    P3.17-009 - A Prospective Clinical Study of MicroRNA Expression Profiling of Bronchoalveolar Lavage Fluids and Sputum as a Means to Distinguish Early Stage Non-Small Cell Lung Cancer Cases From Cancer-Free Controls (ID 3403)

    09:30 - 09:30  |  Author(s): J.O. Kim
    • Abstract

    Background
    MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis and miRNA expression profiling is an emerging tool for the early detection of malignancy. We assessed the ability of microRNA (miRNA) expression profiling of bronchoalveolar lavage (BAL) fluids and sputum samples to distinguish early stage non-small cell lung cancer (NSCLC) cases from cancer-free controls.

    Methods
    The expression levels of 3 miRNAs (miR-21, miR-210, miR-372) were quantified in BAL fluids and sputum, normalized to an endongenous control (U6) relative to a MRC-5 reference sample, using RNA reverse transcription and Quantitative real-time Polymerase Chain Reaction (RT-qPCR). All sputum samples were collected by a single spontaneous expectoration while BAL fluids were obtained just prior to surgical resection. Unsupervised hierarchical cluster analysis was performed on the experimental-normalized miRNA expression profiles using within-group linkage and cosine correlation similarity.

    Results
    From April 2011 to January 2012, twenty-one eligible cases and 10 controls were entered into this study. The median age of cases was 70 years of which 17 were male and 4 were females. Thirteen cases had adenocarcinoma, five had squamous cell carcinoma, and 3 had large cell carcinoma. Twelve cases had stage I and 9 had stage II NSCLC. The median short axis diameter of the primary tumour amongst cases was 1.6 cm. With exception of one case, endobronchial lesions were not detected on inspection by flexible bronchoscopic examination prior to BAL fluid collection. The vast majority of cases were smokers (20/21). The median age of the control group was 58.5 and five were healthy without active medical conditions while five had COPD. Six controls had prior or current histories of smoking while 4 were never smokers. Cluster analysis of the miRNA expression profiles of BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls yielded a diagnostic sensitivity of 85.7% and specificity of 100%. Cluster analysis of sputum samples from the same 21 NSCLC cases and 10 cancer-free controls yielded a diagnostic sensitivity of 67.8% and specificity of 90%. A cosine similarity analysis of matched pairs of concordant and discordant BAL and Sputum samples was conducted and indicated that sampling error accounted for 6 of the 7 false negative results. This suggests that triplicate sputum sample collection could improve the overall sensitivity of this method for use as a safe, non-invasive screening test for NSCLC or as a pre-screening test to select patients for low-dose CT screening.

    Conclusion
    Hierarchical cluster analysis of 3 expressed miRNAs obtained from sputum and brochoalveolar lavage samples are highly specific and relatively sensitive methods for the timely diagnosis of early stage NSCLC. Larger, population-based studies are necessary for further validation of this promising approach in both the diagnostic and screening setting.