Author of

• 18972

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  P2.02 - Biology/Pathology (ID 616)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Biology/Pathology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23271

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    P2.02-073 - Cytoplasmic Mislocalization of ECT2 Protein Is Associated with Poor Prognosis in Lung Adenocarcinoma (ID 8430)

    09:30 - 09:30  |  Presenting Author(s): Zeinab Kosibaty
    • Abstract

    Background:
    Lung cancer is the most lethal malignancy in worldwide. We have previously compared genetic abnormality profiles in early-stage lung adenocarcinoma using array-comparative genomic hybridization (CGH) and found that Epithelial cell transforming sequence 2 (ECT2) amplification and overexpression a new prognostic marker in early-stage lung adenocarcinoma (Cancer Science, 2014). ECT2 is an oncogene that is overexpressed in several types of human cancer and has tumorigenic activity. ECT2 is localized in the nucleus of normal cells, and its function is associated with cytokinesis. In cancer cells, ECT2 exists in not only nucleus but also cytoplasm. However, cytoplasmic ECT2 is thought to promote tumor growth and invasion. In the present study, we aimed to explore the expression of cytoplasmic ECT2 and to assess its functional and prognostic significance in lung adenocarcinoma. First, we examined the subcellular localization of the ECT2 protein in lung adenocarcinoma cells. Subsequently, we investigated the biological significance of cytoplasmic ECT2 that mediated its phosphorylation state. Finally, we examined the clinicopathological attributes of cytoplasmic ECT2 in terms of patient outcome.
    
    Method:
    ECT2 expression was evaluated in an immortalized lung epithelial cells (PL16B) and eight lung adenocarcinoma cell lines Calu-3, A549, RERF-LC-KJ, NCI-H1650, PC-9, NCI-H23, NCI-H1975, and HCC827 using Immunoblotting, RT-PCR, Immunofluorescence, and Immunohistochemistry. In order to assess the clinicopathologic characteristics of cytoplasmic ECT2, we examined 50 cases of surgical specimens lung adenocarcinoma by immunohistochemistry. Twenty fresh scraping samples of lung adenocarcinoma were also used to evaluate the expression of Phosho-ECT2 (T790). The Kaplan–Meier method and Cox regression analyses represent the prognostic significance of cytoplasmic ECT2 in lung adenocarcinoma.
    
    Result:
    We found that ECT2 expressed in eight lung adenocarcinoma at variable degree levels. In PL16B cells, ECT2 was localized in the nucleus, whereas in lung adenocarcinoma cell lines ECT2 distributed in both the cytosol and the nucleus. Importantly, overexpression of ECT2 leads to aberrant cytoplasmic localization in lung adenocarcinoma cells. We also found that cytoplasmic ECT2 was phosphorylated and accumulated at the cell membrane in lung adenocarcinoma cell lines and surgical specimens. The phosphorylated form of ECT2 was reported to correlate with malignant attributes of lung adenocarcinoma and our clinical analysis showed that cytoplasmic ECT2 expression was significantly associated with poor outcome (OS; P=0.002, DFS; P =0.001), and was an independent prognostic factor in lung adenocarcinoma.
    
    Conclusion:
    We demonstrate that aberrant localization of ECT2 to the cytoplasm is a specific feature of lung adenocarcinoma, and provide a new potential prognostic biomarker in lung adenocarcinoma.