Implications of different cell death patterns for prognosis and immunity in lung adenocarcinoma

In recent years, lung adenocarcinoma (LUAD) has become a focus of attention due to its low response to treatment, poor prognosis, and lack of reliable indicators to predict the progression or therapeutic effect of LUAD. Different cell death patterns play a crucial role in tumor development and are promising for predicting LUAD prognosis. From the TCGA and GEO databases, we obtained bulk transcriptomes, single-cell transcriptomes, and clinical information. Genes in 15 types of cell death were analyzed for cell death index (CDI) signature establishment. The CDI signature using necroptosis + immunologic cell death-related genes was established in the TCGA cohort with the 1-, 2-, 3-, 4- and 5-year AUC values were 0.772, 0.736, 0.723, 0.795, and 0.743, respectively. The prognosis was significantly better in the low CDI group than in the high CDI group. We also investigated the relationship between the CDI signature and clinical variables, published prognosis biomarkers, immune cell infiltration, functional enrichment pathways, and immunity biomarkers. In vitro assay showed that HNRNPF and FGF2 promoted lung cancer cell proliferation and migration and were also involved in cell death. Therefore, as a robust prognosis biomarker, CDI signatures can screen for patients who might benefit from immunotherapy and improve diagnostic accuracy and LUAD patient outcomes.