TKI resistant-based prognostic immune related gene signature in LUAD, in which FSCN1 contributes to tumor progression

Drug resistance reflects the evolution of tumors, which is the main cause of recurrence and death. Currently, EGFR-TKI treatment is the first-line therapy for lung adenocarcinoma (LUAD) patients. Although EGFR-TKI achieved good effects at the beginning, most of the LUAD patients eventually acquired resistance. Therefore, it's urgently need to develop a strong criterion for identifying these patients who may benefit from additional therapy. In this study, we established a three TKI resistant-related gene signature (DDIT4, OAS3, FSCN1), and determined that's an accuracy, independent and specific prognostic model for LUAD patients. Patients categorized as high-risk by this signature showed more sensitive to chemotherapy, and exhibited higher expression of common immune checkpoints such as PD-L1/B7H3/PD-L2/IDO1. Moreover, these patients were characterized by increased infiltration of M0 macrophage and activated memory CD4⁺ T cells. The expression and prognostic values of DDIT4, FSCN1 and OAS3 were further confirmed in clinical data. In addition, experimental data showed that FSCN1 promoted LUAD development via PI3K/AKT signaling. In conclusion, this signature is highly predictive of prognostic in LUAD patients, and may serve as a powerful prediction tool for LUAD patients to further choose chemo- and immunotherapies.