Article Text
Abstract
Introduction Endometrial cancer (EC) is the most common gynecological cancer. Although multidisciplinary therapy including surgery improves prognosis of early-stage cases, that of refractory cases remains poor. In this study, we aimed to investigate potential biomarkers for predicting prognosis in refractory cancer.
Methods We performed iTRAQ-based comprehensive protein analysis using EC tissue before treatment that turned to refractory or responsive cases. To evaluate the function of IGF2BP2 in cell proliferation of EC cells, we generated IGF2BP2 knockdown cells using siRNA and shRNA.
Results Protein analysis identified 2299 proteins, and in refractory cases, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was the highest expression protein. Survival analysis of 119 EC cases by immunohistochemistry showed that high expression of IGF2BP2 was a poor prognostic factor (p<0.05). Interestingly, analysis of TCGA dataset revealed the correlation between elevated IGF2BP2 mRNA level and poor prognosis (p<0.05). Furthermore, we demonstrated that knockdown of IGF2BP2 in EC cell lines by siRNA and shRNA suppressed cell proliferation, respectively (p<0.05). Moreover, analysis of publicly available protein datasets of EC samples suggested that high expression of IGF2BP2 was associated with activation of NF-KB pathway. Finally, we demonstrated that NF-KB activation was suppressed in IGF2BP2 knockdown cells.
Conclusion/Implications IGF2BP2 is highly expressed in refractory EC tissue and contributes cell proliferation via the NF-κB pathway and poor prognosis.