Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma:Based on muti-omics analysis and vitro assay  

作　　者：HONGYUAN LIANG YANQIU LI YONGGANG QU LINGYUN ZHANG 

机构地区：[1]Department of Radiology,Shengjing Hospital of China Medical University,Shenyang,China [2]Department of Nephrology,The First Affiliated Hospital of China Medical University,Shenyang,China [3]Department of Clinical Medicine,China Medical University,Shenyang,China [4]Department of Medical Oncology,The First Hospital of China Medical University,Shenyang,China

出　　处：《Oncology Research》2024年第2期393-407,共15页肿瘤学研究（英文）

基　　金：National Natural Science Foundation of China(Grant No.81273297);Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).

摘　　要：Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two

关 键 词：Lung adenocarcinoma Programmed cell death Iron-death Drug sensitivity Cancer therapy 

分 类 号：R735.2[医药卫生—肿瘤]