Abstract 5566: Comprehensive protein and genomic analysis demonstrate IGF2BP2 promotes cell proliferation via NF-kB signaling pathway in endometrial cancer

Introduction: Endometrial cancer (EC) is the most common gynecological cancer. While multidisciplinary therapy including surgery and chemotherapy improves the prognosis, that of refractory cases remains poor. In this study, we aimed to investigate the new treatment target and predictive marker for treatment of refractory EC using comprehensive protein analysis and TCGA genomic data. Materials and Methods: We performed iTRAQ-based comprehensive protein analysis using EC tissue samples before treatment, and compared protein expression data of refractory and responsive cases. To evaluate the function of Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) which is highly expressed in refractory EC, we generated IGF2BP2 knockdown (KD) EC cells using siRNA and shRNA and evaluated cell proliferation after IGF2BP2 KD in vitro and in vivo. Moreover, we investigated signaling pathway regulated by IGF2BP2 using protein dataset. Finally, we measured IGF2BP2 cfDNA in the case of EC before and after treatment. Results: iTRAQ-based comprehensive protein analysis identified 2,299 proteins, and IGF2BP2 had the highest expression in refractory EC. High expression of IGF2BP2 in refractory EC was validated by immunohistochemistry. TCGA data analysis revealed the significant correlation between elevated IGF2BP2 mRNA levels and poor prognosis of EC (p < 0.01). Furthermore, we demonstrated that IGF2BP2 KD in EC cell lines significantly suppressed cell proliferation in vitro and tumor growth in vivo (p < 0.01, respectively). Moreover, analysis of protein datasets (Cell. 2020) of EC showed that high expression of IGF2BP2 was associated with activation of NF-kB pathway, and IGF2BP2 KD inactivated NF-kB in vitro. Finally, we demonstrated that IGF2BP2 cfDNA was decreased after complete surgery for EC. Conclusion: IGF2BP2 is highly expressed in refractory EC and contributes to cell proliferation via NF-kB pathway and poor prognosis. Citation Format: Hiroki Kurahashi, Yuko Watanabe, Kosuke Hiramatsu, Tatsuo Masuda, Mamoru Kakuda, Satoshi Nakagawa, Tadashi Iwamiya, Shinya Matsuzaki, Yutaka Ueda. Comprehensive protein and genomic analysis demonstrate IGF2BP2 promotes cell proliferation via NF-kB signaling pathway in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5566.