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

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 x 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. British Journal of Cancer (2012) 107, 1327-1336. doi:10.1038/bjc.2012.410 www.bjcancer.com Published online 18 September 2012 (C) 2012 Cancer Research UK