Role of the angiogenic components, VEGFA, FGF2, OPN and RHOC, in urothelial             cell carcinoma of the urinary bladder.
The objective of this study was to analyze the expression profile of the             angiogenic components, vascular endothelial growth factor-A (VEGFA), basic fibroblast             growth factor-2 (FGF2), osteopontin (OPN) and ras homolog gene family, member C             (RHOC), in urothelial cell carcinoma (UCC) of the urinary bladder and to examine             their role as candidate diagnostic biomarkers. Using qPCR, 77 samples of UCC of             the urinary bladder and 77 matched tumor-associated normal samples were investigated             to determine the expression of the four angiogenic components. The correlation             between gene expression, patient survival and pathological features of the tumors             was also examined. The VEGFA and OPN transcript levels were greater in the bladder             cancer tissue than in the normal urothelium (P<0.001). Patients with higher             VEGFA mRNA levels showed a tendency towards shorter cancer-specific survival.             OPN levels showed a gradual increase, the lowest levels being found in non-invasive             carcinoma and the highest in muscle invasive tumors. Elevated OPN levels indicated             poor prognosis in connection with advanced disease stage (P<0.001). Both superficially             invasive and muscle invasive tumors had significantly higher FGF2 levels compared             to the control tissues (P=0.018 and P=0.050, respectively). Moreover, FGF2 was             significantly higher in the metastatic vs. the non-metastatic tumors (P=0.0097).             FGF2 levels exhibited a trend towards a correlation with worse patient survival.             RHOC mRNA levels were higher in muscle invasive compared to superficially invasive             tumors, as well as in grade III vs. grade I/II tumors. Furthermore, we detected             worse overall survival for patients with high RHOC expression levels. VEGFA and             FGF2 exhibited the best linear combination in the ROC curves for specificity and             sensitivity. Thus, VEGFA and FGF2 may serve as candidate biomarkers for diagnostic             purposes. Higher OPN expression may be used as a potential biomarker to predict             patient survival relative to advanced tumor stage. However, further studies are             required to investigate its role in urinary bladder carcinogenesis.
Laboratory of Virology, Medical School, University of Crete,                     71110 Heraklion, Crete, Greece.
Apostolos
A
Zaravinos
Dimitrios
D
Volanis
George I
GI
Lambrou
Dimitris
D
Delakas
Demetrios A
DA
Spandidos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics*; D011379:Prognosis; D012372:ROC Curve; D012016:Reference Values; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D020741:rho GTP-Binding Proteins / Q000235:genetics*; D000075024:rhoC GTP-Binding Protein
D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D053495:Osteopontin; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein