Author of

• 11481

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  P2.02 - Poster Session 2 - Novel Cancer Genes and Pathways (ID 148)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11482

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    P2.02-001 - MED12, a component of the transcriptional MEDIATOR complex, and STAT3 influence outcome to platinum-based chemotherapy in patients (p) with advanced non-small-cell lung cancer (NSCLC) (ID 323)

    09:30 - 09:47  |  Author(s): D. Morales-Espinosa
    • Abstract

    Background
    MED12 negatively regulates TGF-b receptor signaling. Loss of MED12 induces an EMT-like phenotype associated with chemotherapy resistance. IDO and IL6 activate the JAK2/STAT3 signaling pathway, which – together with NFkB (RelA) signaling – is often altered in lung cancer. BIM could influence response to chemotherapy. We have examined these components and KRAS mutations in NSCLC tumor samples and correlated results with progression-free survival (PFS).

    Methods
    The mRNA expression of MED12, IDO, JAK2, STAT3, RelA and BIM was examined in microdissected tumor samples from p with stage IV NSCLC. mRNA levels were assessed by RT-PCR and categorized by terciles (high vs low/intermediate). KRAS mutations were assessed by high resolution melting.

    Results
    A total of 55 p with performance status (PS) 0-1, treated with platinum plus either gemcitabine or pemetrexed: median age, 62 years; 27.6% females; 84.2% smokers; 66% adenocarcinoma; 16% with KRAS mutations. There was no correlation between gene expression levels and KRAS mutation status. In the multivariate analysis, including gene expression levels, histology and PS, only MED12 and STAT3 were associated with PFS (low MED12: HR=11.6, P=0.005; high STAT3: HR=6.5, P=0.01). HR for low BIM expression was 2.4 (P=0.16). None of the markers were associated with overall survival.

    Conclusion
    To the best of our knowledge, this is the first time that low expression of MED12 with significantly shorter PFS in NSCLC p receiving platinum-based chemotherapy. MED12 could be a new biomarker of chemoresistance and inhibition of TGF-bR signaling can restore chemotherapy response in patients with low MED12.