Abstract 4824: Intracellular ferritin expression levels regulate growth and resistance to ferroptosis in pancreatic cancer cell lines

Abstract Background: Pancreatic cancer is one of the cancers with the highest mortality rate, and it is important to develop effective treatments and elucidate prognostic factors. It has been reported that elevated serum ferritin is associated with the prognosis of pancreatic cancer. However, there are few reports on how ferritin in pancreatic cancer tissue acts in pancreatic cancer. Ferritin heavy chain (FTH) is a major component of ferritin, which stores iron and plays a role in suppressing iron-induced generation of reactive oxygen species. In this study, we aimed to examine the expression level of FTH in pancreatic cancer cells and its prognostic and cell biological roles. Methods: We performed immunostaining of FTH in pancreatic cancer tissue specimens operated on at our hospital and classified the expression level of FTH by scoring the immunostaining intensity and staining rate. The expression levels and prognosis were then evaluated. The overexpression and knockout strains of FTH were generated using a human pancreatic cancer cell line (MIAPaCa-2), and their proliferative and stress tolerance abilities were compared with those of the control group. Results: Immunostaining of 149 pancreatic cancer surgical specimens showed that the group with high FTH had a significantly shorter overall survival rate than the group with low FTH (5-year survival rate; 16.8% vs. 36.9%, p = 0.018). In multivariate analysis, high FTH expression was also a prognostic factor: in vitro, cell lines overexpressing FTH had enhanced proliferative potential compared to controls, while knockout lines were suppressed. In addition, the knockout lines showed decreased resistance to RSL-3, an inducer of ferroptosis. Additional studies are currently underway to examine resistance to other drugs and the production of reactive oxygen species in the cells. Conclusion: In pancreatic cancer, high ferritin expression is associated with worse prognosis and may enhance cell proliferation and stress tolerance, and might be a new treatment or biomarker. Citation Format: Masataka Maruno, Yo-hei Kanamori, Takashi Matsumoto, Yuta Shiraishi, Toru Takematsu, Tatsunori Miyata, Kosuke Mima, Shigeki Nakagawa, Hidetoshi Nitta, Hiromitsu Hayashi, Toshiro Moroishi, Hideo Baba. Intracellular ferritin expression levels regulate growth and resistance to ferroptosis in pancreatic cancer cell lines. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4824.