关键词: PHLPP2, EGFR+TP53共突变, 肺腺癌, 疗效, 铁死亡

Abstract: Objective To investigate the relationship between the PHLPP2 and the efficacy of targeted combined chemotherapy as well as ferroptosis in patients with advanced lung adenocarcinoma (LUAD) harboring EGFR+TP53 co-mutations. Methods Data of 98 patients with advanced LUAD with EGFR+TP53 co-mutation treated with targeted combination chemotherapy from August 2018 to August 2023 were reviewed. The PHLPP2 variations were analyzed and divided into poor prognosis group (n=47) and good prognosis group (n=51) according to prognosis. The dose-response relationship between ferroptosis indicators and poor prognosis was analyzed by restricted cubic spline (RCS) model. The levels of ferroptosis indicators in different PHLPP2 mutations and their relationship with poor prognosis were compared. Results PHLPP2 mutation rate was 30.61%, mainly missense mutation and point mutation. Serum ferritin (SF), malondialdehyde (MDA) and reactive oxygen species (ROS) in poor prognosis group were lower than those in good prognosis group (P＜0.05), and glutathione peroxidase 4 (GPX4), glutathione (GSH) and PHLPP2 mutants in poor prognosis group were higher than those in good prognosis group(P＜0.05). The risk of poor prognosis was correlated with SF, GPX4, GSH, MDA and ROS in a nonlinear dose-response relationship (P_{for non linear}＜0.05). SF, MDA and ROS of wild type were higher than those of mutant type (P＜0.05), GPX4 and GSH were lower than those of mutant type (P＜0.05). There were differences in poor prognosis between different PHLPP2 and different ferroptosis indicators (P＜0.05). Conclusions PHLPP2 mutation affects the clinical efficacy of targeted combination chemotherapy in the treatment of advanced LUAD with EGFR+TP53 co-mutation, and is associated with ferroptosis.

Key words: PHLPP2, EGFR+TP53 co-mutation, lung adenocarcinoma, efficacy, ferroptosis