British Journal of Cancer - Individuality in FGF1 expression significantly influences platinum resistance and progression-free survival in ovarian cancer

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British Journal of Cancer - Individuality in FGF1 expression significantly influences platinum resistance and progression-free survival in ovarian cancer

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British Journal of Cancer advance online publication 18 September 2012; doi: 10.1038/bjc.2012.410

Individuality in FGF1 expression significantly influences platinum resistance and progression-free survival in ovarian cancer

G Smith¹, M T H Ng^1,5, L Shepherd^1,5, C S Herrington¹, C Gourley², M J Ferguson³ and C R Wolf^1,4

1. ¹Division of Cancer Research, Medical Research Institute, University of Dundee, Dundee, UK
2. ²Edinburgh Cancer Research Centre, MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh EH2 2XR, UK
3. ³Tayside Cancer Centre, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK
4. ⁴CRUK Molecular Pharmacology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK

Correspondence: Dr G Smith, E-mail: g.smith@dundee.ac.uk

⁵These authors contributed equally to this work.

Received 4 July 2012; Revised 14 August 2012; Accepted 14 August 2012
Advance online publication 18 September 2012

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Abstract

• Background:
• Methods:
• Results:
• Conclusion:
• Materials and methods
• Results
• Discussion
• References
• Acknowledgements
• Figures and Tables

Background:

  

Ovarian cancer is frequently advanced at presentation when treatment is rarely curative. Response to first-line platinum-based chemotherapy significantly influences survival, but clinical response is unpredictable and is frequently limited by the development of drug-resistant disease.

Methods:

  

We used qRT–PCR analysis to assess intertumour differences in the expression of fibroblast growth factor 1 (FGF1) and additional candidate genes in human ovarian tumours (n=187), and correlated individuality in gene expression with tumour histology, chemotherapy response and survival. We used MTT assays to assess platinum chemosensitivity in drug-sensitive and drug-resistant ovarian cell lines.

Results:

  

Marked intertumour differences in gene expression were observed, with each tumour having a unique gene expression profile. Nine genes, including FGF1 (P=1.7 × 10⁻⁵) and FGFR2 (P=0.003), were differentially expressed in serous and nonserous tumours. MDM2 (P=0.032) and ERBB2 (P=0.064) expression was increased in platinum-sensitive patients, and FGF1 (adjusted log-rank test P=0.006), FGFR2 (P=0.04) and PDRFRB expression (P=0.037) significantly inversely influenced progression-free survival. Stable FGF1 gene knockdown in platinum-resistant A2780DPP cells re-sensitised cells to both cisplatin and carboplatin.

Conclusion:

  

We show for the first time that FGF1 is differentially expressed in high-grade serous ovarian tumours, and that individuality in FGF1 expression significantly influences progression-free survival and response to platinum-based chemotherapy.

Keywords:

fibroblast growth factors; ovarian cancer; survival; chemotherapy; platinum drugs