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  P3.11 - Screening and Early Detection (Not CME Accredited Session) (ID 977)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall

  • 27611

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    P3.11-01 - Methylation Markers That Correlate with Occult Lymph Node Metastases of NSCLC and a Preliminary Prediction Model (ID 13962)

    12:00 - 13:30  |  Author(s): Jianbing Fan
    • Abstract
    • Slides

    Background
    

    Lymph node (LN) metastasis status is the most important prognostic factor and determines the treatment strategy. The current imaging approaches are not sufficiently precise to diagnose occult LN metastasis before surgery, while the invasive biopsy fails to be widely used. Therefore, more precise and non-invasive methods are warranted to determine the lymph node status preoperatively and lead to appropriate treatment strategy. Methylation alteration is an optimal candidate to trace the signal from early stage tumors due to its early existence, multiple loci and stability in blood. To build a diagnostic tool, we shall firstly screen and identify a set of plasma methylation markers.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    High-throughput targeted methylation sequencing was performed on plasma and matched tissue samples from a cohort of 134 lung cancer patients with a primary lesion less than 3 cm in diameter. The methylation profiles were compared between patients with and without occult LN metastases. A preliminary prognostic model was built by random forest by integrating both top 5 hypermethylated genes and top 5 hypomethylated genes.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Within this cohort, 22 cases were found to have occult LN metastases found by pathological examination. Thus, we selected the other 22 cases without occult LN metastasis by matching gender, age, smoking history and tumor histology. Hypermethylation on 32 genes, such as TNFRSF1B, DMRTA2, VAV3-AS1, HIST3H2A, PALD1, NKX2-3, MAP3K12, MAPK10, were identified between the two groups. Hypomethylation on 20 genes, such as RAB42, KCNN3, UBE2L6, RARG, CRY1, MTUS2, TMEM179, MEGF11, were also detected. 25% (13 out of 52 genes) of these markers could be found in the matched tissue samples. The AUC of ten fold cross validation of the preliminary prediction model is 0.86.

    

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    We found some specific plasma methylation markers for occult LN metastasis of NSCLC. Further efforts should be made in establishing a non-invasive blood diagnostic tool.

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