Author of

• 14490

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  P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14584

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    P2.04-094 - Exosomal MiRNA Analysis of Non-Small Cell Lung Cancer (NSCLC) Liquid Biopsies. Mirror of the Disease Status?: Proof of Concept Study (ID 1395)

    09:30 - 09:30  |  Author(s): S. Goethals
    • Abstract
    • Slides

    Background:
    The discovery of the alterations in EGFR, c-Met or ALK in NSCLC has driven the development of targeted-drug therapy using tyrosine kinase inhibitors (TKIs). To optimize the use of these TKIs, the discovery of new biomarkers for early detection and disease progression is needed. The exosomes extracted from blood samples could be non-invasive and regularly updated biomarkers. Here we analyze selected exosomal miRNAs to evaluate its biomarker potential in NSCLC.
    
    Methods:
    1 ml of serum/plasma sample from 11 NSCLC patients, with different mutations and treatments (and 6 healthy donors as controls), were used as exosome sources. Exosome were isolated through commercial-kit or D~2~O/sucrose density-gradient ultracentrifugation. After exosome characterization (Western-Blot, Transmission Electron Microscopy) a panel of miRNAs (30b-5p, 30c-5p, 103,195,221-3p,222-3p), correlated with NSCLC disease (Garofalo et al, 2013), was analyzed. The miRNAs profile analysis was performed through TaqMan Real-Time PCR and mir-1228-3p was used as endogenous control. The data was processed according to the formula 2[-ΔΔct]. Control values are used as baseline and results are shown in logarithmic scale (figure).
    
    Results:
    Patients without molecular alterations (WMA): The levels of miR-30b-5p/30c-5p/103/221-3p/222-3p were down-regulated relative to the healthy controls. The patient with docetaxel treatment (P2) has an increased down-regulation of these miRNAs compared to the non-treated patient (P1). Patient with BRAF G464V: We observed an increased up-regulation of miR-30b-5p/30c-5p/103/221-3p/222-3p just after stopping Erlotinib treatment (P4a) compared with one month after the treatment (P4b). Patients with C-Met 3+ over-expression: We detected an increase of expression of miR-30b-5p/30c-5p and a decrease of expression of mir221-3p/222-3p in a patient treated with Crizotinib (P6) compared to a non-treated patient (P5). Patients with EGFR (exon 19 del): We observed a decrease of expression of mir221-3p/222-3p in a patient treated with Afatinib beyond progression (P8) compared to a non-treated patient (P7). Patients with ALK t(2p23): We detected a decrease of expression of miR-30b-5p/30c-5p/103 compared to healthy controls. No differences between treated (P9-P11) and non-treated (P3) patients were observed. Nevertheless, mir221-3p/222-3p differs significantly between patients treated with Ceritinib one week (P10) and one month (P11) after the treatment was started.
    
    Conclusion:
    This panel of exosomal miRNAs derived from patients with varying mutations is responsive to different treatments. The down-regulation of miR-30b-5p/30c-5p in exosomes of patients with WMA and ALK t(2p23) mutations, mirrored the reported low levels of these miRNAs in NSCLC tissue (Zhong et al.,2014). Follow-up analysis to correlate clinical progression and exosome miRNAs profile is currently ongoing. Figure 1
    
    
    
    

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