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

Abstract:

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.

journal_name

Br J Cancer

authors

Smith G,Ng MT,Shepherd L,Herrington CS,Gourley C,Ferguson MJ,Wolf CR

doi

10.1038/bjc.2012.410

subject

Has Abstract

pub_date

2012-10-09 00:00:00

pages

1327-36

issue

8

eissn

0007-0920

issn

1532-1827

pii

bjc2012410

journal_volume

107

pub_type

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