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K. Ishioka



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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
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      P2.02-005 - Expression of fibroblast growth factor-9 is associated with poor prognosis of resected non-small cell lung cancer patients (ID 981)

      10:38 - 10:55  |  Author(s): K. Ishioka

      • Abstract

      Background
      Fibroblast growth factor (FGF) family consists of at least 23 polypeptides which have important functions in embryonic development, tissue repair, and tumorigenesis. Recent studies have shown that the activation of FGF9 is associated with pathogenesis of several cancers. In the lungs, FGF9 was highly expressed in adenocarcinoma by immunohistochemistry, and disturbing FGF9 function reduced the proliferation of lung adenocarcinoma. However, its clinicopathological and biological significance in non-small cell lung cancer (NSCLC) is unclear. The purpose of this study is to clarify the characteristics of FGF9-expressing NSCLC.

      Methods
      Using a cDNA microarray data set for 90 surgically resected NSCLC and corresponding non-tumorous lung tissue samples, we analyzed the relationship between the expression of FGF9 and their clinicopathological characterisitics. Also, we validated FGF9 expression by quantitative RT-PCR, and immunohistochemistry at protein level. Associations between FGF9 expression and clinicopathological factors were assessed by the χ2 test and Mann-Whitney U-test. Log-rank test was applied for survival analysis, and Kaplan-Meyer curve (Fig.1) was drawn. Multivariate analyses of the influence of variables on overall survival were performed with using Cox proportional hazards model.

      Results
      Nine out of 90 (10%) NSCLC had “high” FGF9 expression compared with corresponding non-cancerous lung tissues. Histologically, 5 out of 9 FGF9-high NSCLC were adenocarcinoma, and there was no squamous cell carcinoma. The correlations between FGF9 expression and sex, smoking history or clinical stage were not observed. On the other hand, postoperative recurrence rates and 3-year survival rates were 56% vs. 36% (p=0.033) and 44% vs. 88% (p=0.001) for FGF9-high vs. -low NSCLC patients, respectively. The overall survival of the patients with high-FGF9 expression was significantly worse compared that with FGF9-low NSCLC patients (p<0.001). At protein level, FGF9 expression (immunohistochemistry) was significantly higher in FGF9-high mRNA group compared with FGF9-low group. FGF9 was confirmed to be expressed in cancer cells in these resected NSCLC tissues, and localized in cytoplasm of the cells. Figure 1

      Conclusion
      FGF9 is highly expressed in a subset of lung adenocarcinoma, and is associated with poor prognosis.