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

Yang Zhou; Weitong Gao; Yu Xu; Jiale Wang; Xueying Wang; Liying Shan; Lijuan Du; Qingyu Sun; Hongyan Li; Fang Liu

doi:10.1038/s41698-023-00456-y

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

NPJ Precis Oncol. 2023 Nov 15;7(1):121. doi: 10.1038/s41698-023-00456-y.

Authors

Yang Zhou^#¹, Weitong Gao^#¹, Yu Xu^#², Jiale Wang¹, Xueying Wang³, Liying Shan¹, Lijuan Du¹, Qingyu Sun¹, Hongyan Li¹, Fang Liu⁴

Affiliations

¹ Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150081, Harbin, China.
² College of Resources and Environment, Northeast Agricultural University, 150030, Harbin, China.
³ Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, 410008, Changsha, China.
⁴ Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150081, Harbin, China. fangliu@hrbmu.edu.cn.

^# Contributed equally.

Abstract

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.