Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients

Background: Lung adenocarcinoma (LUAD) is an extraordinarily malignant tumor, with rapidly increasing morbidity and poor prognosis. Immunotherapy has emerged as a hopeful therapeutic modality for lung adenocarcinoma. Furthermore, a prognostic model (based on immune genes) can fulfill the purpose of early diagnosis and accurate prognostic prediction.

Methods: Immune-related mRNAs (IRmRNAs) were utilized to construct a prognostic model that sorted patients into high- and low-risk groups. Then, the prediction efficacy of our model was evaluated using a nomogram. The differences in overall survival (OS), the tumor mutation landscape, and the tumor microenvironment were further explored between different risk groups. In addition, the immune genes comprising the prognostic model were subjected to single-cell RNA sequencing to investigate the expression of these immune genes in different cells. Finally, the functions of BIRC5 were validated through in vitro experiments.

Results: Patients in different risk groups exhibited sharply significant variations in OS, pathway activity, immune cell infiltration, mutation patterns, and immune response. Single-cell RNA sequencing revealed that the expression level of BIRC5 was significantly high in T cells. Cell experiments further revealed that BIRC5 knockdown markedly reduced LUAD cell proliferation.

Conclusion: This model can function as an instrumental variable in the prognostic, molecular, and therapeutic prediction of LUAD, shedding new light on the optimal clinical practice guidelines for LUAD patients.