Abstract 5257: FGF9 overexpression promotes tumorigenic potential of non-small cell lung cancer (NSCLC) cells, and is associated with poor prognosis in NSCLC patients.

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Abstract Background. Fibroblast growth factor 9 (FGF9) is a member of the FGF family, which modulates cell proliferation, differentiation and motility. Recent studies show that activation of FGF signals including FGF9 is associated with pathogenesis of several cancers. In lung cancer, some reports showed that FGF9 indirectly promoted the growth of lung adenocarcinoma and the intensity of FGF9 staining was positively correlated with the status of disease and the degree of lymph node metastasis in lung adenocarcinoma patients. However, the direct effect of FGF9 on the development and growth of lung cancer has not been clear. Purpose. The purpose of this study is to clarify the role of FGF9 in NSCLC. Method. First, we have performed in vitro analysis to clarify the role of FGF9 in NSCLC. FGF9 was introduced by retroviral infection to make stable cell lines. The cell lines which express no or low FGF9 were selected for the study, namely A549, PC9 and H1975. Overexpression of FGF9 in these cells was confirmed at mRNA and protein levels. Tumorigenic potential was evaluated by soft agar colony formation assay. The effect on proliferation of NSCLC cells was evaluated by MTS proliferation assay. Next, patients survival analysis was also performed to evaluate the effect of FGF9 on the prognosis of NSCLC patients. NSCLC specimens were obtained from 91 patients who underwent surgical resection at Department of Thoracic Surgery, Keio University Hospital from 2001 through 2006 with written informed consent. We have performed cDNA microarray gene expression analysis. Patient survival data was evaluated by genes expression profile. Results. Of the cells studied, A549 with FGF9 overexpression (A549-FGF9) cells significantly increased the anchorage independent colony formation ability compared with A549-empty cells. The numbers of the colonies were significantly higher in A549-FGF9, and the size of the colonies was bigger compared with A549-empty. For patient study, we found 10 out of 91 (11.0%) NSCLC patients overexpressed FGF9. We found FGF9 overexpression was associated with significantly worse prognosis (p=0.001). While none of other FGFs and FGFRs was associated with the prognosis of the patients. Three-year survival rate of FGF9-high patient group and FGF9-low patient group were 40% and 88% respectively. The rate of relapse was significantly higher in FGF9-high patients compared with FGF9-low patients, 60% vs 36.2% (p=0.016). Conclusion. Our in vitro and clinical data indicate that FGF-9 may promote tumorigenic potential, and can be a prognostic indicator in NSCLC patients. Citation Format: Kota Ishioka, Kenzo Soejima, Hiroyuki Yasuda, Keiko Ohgino, Satoshi Yoda, Takashi Sato, Junko Hamamoto, Daisuke Arai, Tetsuo Tani, Aoi Kuroda, Katsuhiko Naoki, Tomoko Betsuyaku. FGF9 overexpression promotes tumorigenic potential of non-small cell lung cancer (NSCLC) cells, and is associated with poor prognosis in NSCLC patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5257. doi:10.1158/1538-7445.AM2013-5257