Author of

• 18974

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  P3.02 - Biology/Pathology (ID 620)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 24019

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    P3.02-071 - Statins May Improve the Prognosis of Patients with Lung Adenocarcinoma by Suppressing Mutant p53-Induced EMT (ID 9152)

    09:30 - 09:30  |  Author(s): T. Soawa
    • Abstract

    Background:
    Epithelial-mesenchymal transition (EMT) is known to be pivotal for driving metastasis and recurrence in lung cancer. Some reports have shown statins suppressed EMT by inactivating mutant p53 functions in vitro. Although several clinical trials regarding conventional treatments with statins have been performed, the effect of statins on the prognosis is still controversial. The purpose of the present study is to clarify the impact of statins on EMT and the prognosis of patients with lung adenocarcinoma harboring p53 mutation.
    
    Method:
    Firstly, we transfected wild type p53 or mutant p53 (R175H, R273H) to H1650 cells and administrated simvastatin. We evaluated morphological changes by microscopic measurement and analyzed EMT markers (E-cadherin, vimentin) through western blotting of whole cell lysate. We also analyzed their invasive ability through Matrigel invasion assay. Secondly, a total of 282 lung adenocarcinoma specimens were collected from patients who underwent surgery in our institute from January 2001 to December 2007. We analyzed EMT markers through immunostaining of tumor specimens and we determined p53 mutation by single stranded conformational polymorphism followed by direct sequencing. The association between EMT, p53 mutation status, and statin use as well as the patients’ clinical information was statistically analyzed. Correlations were compared using Pearson's chi-square test and overall survival were compared using the log-rank test.
    
    Result:
    When mutant p53 (R175H, R273H) were transfected, H1650 cells showed EMT like morphological changes. E-cadherin expression was decreased and vimentin expression was increased in H1650 harboring mutant p53 (H1650[mut.p53]). Additionally, H1650[mut.p53] obtained more aggressive invasiveness compared to H1650 harboring wild type p53. However, simvastatin-treated H1650[mut.p53] lost EMT character changes and aggressive invasiveness. According to the medical records, about 20% of the patients took statins (simvastatin, pravastatin, and so on) as a treatment of hyperlipidemia or coronary artery disease. Consistent with the results of in vitro experiments, IHC showed that statin administration was correlated to fewer EMT only in the patients with mutant p53. Moreover, the statin-administrated group showed significantly better survival compared to the non-statin group (p=0.04), which was observed only in the patients with mutant p53.
    
    Conclusion:
    Statins suppressed EMT and improved the prognosis of patients with lung adenocarcinoma in a p53 mutation-dependent manner.