Study On Inhibition Of Epidermal Growth Factor Receptor In Thymoma By RNA Interference

Objective: To investigate the expression level of EGFR in thymoma and its clinical significance in thymoma.To investigate whether RNA interference could induce gene silencing in thymoma cells as well as assess the degree of epidermal growth factor receptor gene silencing and its effect on functional outcome. Methods: The expressin of EGFR was detected and compared using immunohistochemical technique.EGFR mutation statuses were evaluated by PCR and DNA assay.Recombinant adenovirus AdshEGFR were constructed driving by H1 promoter targeted on EGFR utilizing gene recombinant technology.EL-4 cells was transfected with recombinant adenovirus, and the change of EGFR mRNA and proteins were detected, then the proliferation and apoptosis of EL-4 cells were observed. Results: The difference of positive rate of EGFR in thymomas and normal thymuses was very significant.The difference of EGFR positive rate was very significant between Masaoka stage IIII-IV and I and was significant between III-IV and II, but there was no difference between stage I and II. The expression of EGFR of thymoma had no obvious correlation with MG. The EGFR expression intensity was significantly stronger in thymoma with severe MG. EGFR gene mutations were not detected in any of the thymoma and thymic cancer samples using PCR assay.EGFR expression was inhibited in EL-4-H1-EGFR cells by a small hairpin RNA of EGFR. The growth of EL-4 cells transfected specific small hairpin RNA was slow. AdshEGFR could inhibit proliferation of tumor cells and promote their apoptosis. Conclusions: EGFR may play a important role in thymoma progression. EGFR may be considered as a supplementary predictor for Masaoka staging and predict the aggression and progression more accurately. The expression of EGFR in thymic tumours does not rely on mutations in critical functional domains of the EGFR-gene. The specific small hairpin RNA targeting EGFR can inhibit the expression of EGFR protein and proliferation of thymoma cancer cells.It could also promote their apotosis.