Basic fibroblast growth factor (FGF-2) overexpression is a risk factor for esophageal cancer recurrence and reduced survival, which is ameliorated by coexpression of the FGF-2 antisense gene.
OBJECTIVE
The basic fibroblast growth factor (FGF-2) gene is bidirectionally transcribed to generate overlapping sense and antisense (FGF-AS) mRNAs. FGF-AS has been implicated in the post-transcriptional regulation of FGF-2 expression. The aim of this study was to characterize FGF-2 and FGF-AS in esophageal cancer and to correlate their expression with clinicopathologic findings and outcome.


METHODS
Reverse transcription-PCR was used to study FGF-2 and FGF-AS mRNA expression (normalized to glyceraldehyde-3-phosphate dehydrogenase) in 48 esophageal cancers relative to matched histologically normal esophageal epithelia (internal control). We used Cox proportional hazards analysis to calculate hazard ratios for recurrence and survival of patients with underexpression relative to the overexpression of FGF-2 and/or FGF-AS.


RESULTS
Overexpression of FGF-2 mRNA, by comparison with tumors underexpressing FGF-2, was associated with significantly increased risk for tumor recurrence (hazard ratio, 3.80; 95% confidence interval, 1.64-8.76) and reduced overall survival (hazard ratio, 2.11; 95% confidence interval, 1.0-4.58). When the effects of FGF-2 and FGF-AS were considered simultaneously, the association of FGF-2 mRNA overexpression with recurrence and mortality was even more pronounced, whereas FGF-AS mRNA overexpression was associated with reduced risk for recurrence and improved survival.


CONCLUSIONS
Overexpression of FGF-2 mRNA is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer and that these risks are reduced in tumors coexpressing the FGF-AS mRNA. These data support the hypothesis that FGF-AS is a novel tumor suppressor that modulates the effect of FGF-2 expression and may have potential clinical application to the development of novel therapeutic strategies.
Barclay
Christie
C
Department of Physiology, Dalhousie University, Halifax, Nova Scotia, Canada.
Li
Audrey W
AW
Geldenhuys
Laurette
L
Baguma-Nibasheka
Mark
M
Porter
Geoffrey A
GA
Veugelers
Paul J
PJ
Murphy
Paul R
PR
Casson
Alan G
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015999:Multivariate Analysis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016016:Proportional Hazards Models; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2