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ROLE OF IFN-GAMMA AND TWEAK EXPRESSION IN NEOANGIOGENESIS IN COLORECTAL POLYPOID LESIONS
Cesare Ruffolo*2, Luisa Toffolatti2, Marco Massani2, Andromachi Kotsafti1, Anna Pozza2, Marta Campo Dell'Orto2, Luca Maria Saadeh3, Francesco Ferrara2, Stefano Benvenuti2, Angelo Paolo Dei Tos2, Nicolò Bassi2, Marco Scarpa1
1Veneto Institute of Oncology, Padova, Italy; 2Ospedale Ca' Foncello, Treviso, Italy; 3University of Padova, Padova, Italy
Background
VEGF-A and VEGF-C expression in colorectal polypoid lesion are implied in carcinogenesis progression. IFN-gamma and TWEAK molecules seem to have a potential effect on angiogenic factors such as VEGF and FGF. The aim of this study was to assess a possible interplay between IFN-gamma and TWEAK cytokines and VEGF pathway in the different steps of colorectal carcinogenesis.
Methods
A total of 92 subjects with colonic adenoma or cancer who underwent screening colonoscopy or surgery were prospectively enrolled. Polypoid lesion tissue samples were collected and frozen. Real-time reverse transcription polymerase chain reaction for IFN-gamma, TWEAK and VEGF-A mRNA expression was performed. Immunoassays for VEGF-A, VEGF-C, VEGFR-1, VEGFR-2, and VEGFR-3 were also performed. Non-parametric statistics, receiver operating characteristic curve analysis, and logistic multiple regression analysis were used.
Results
IFNgamma and TWEAK mRNA expression was higher in patients with T2 or more advanced colorectal cancer than in those with adenomas or T1 cancer (p<0.001 and p=0.01, respectively). IFNgamma and TWEAK mRNA expression levels directly correlated with VEGF-A mRNA expression levels (rho=0.44, p<0.001 and rho=0.29, p=0.004, respectively). On the contrary, IFNgamma and TWEAK mRNA expression levels inversely correlated with VEGF-C protein levels (rho=-0.29, p=0.04 and rho=-0.31, p=0.03, respectively). Similarly, IFNgamma and TWEAK mRNA expression levels inversely correlated with VEGFR2 protein levels (rho=-0.38, p=0.033 and rho=-0.40, p=0.025, respectively).
Conclusion
This study demonstrated that in colorectal polypoid lesions IFNgamma and TWEAK expression are directly correlated to VEGF-A expression but inversely correlated with VEGFR2 levels. This observation suggests a possible feedback mechanism in the regulation of VEGF-A expression.
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