A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma.
Bo TangLanlin HuTao JiangYunchang LiHuasheng XuHang ZhouMei LanKe XuJun YinChunxia SuCaicun ZhouChuan XuPublished in: International journal of molecular sciences (2022)
Immunotherapy, such as immune checkpoint inhibitors (ICIs), is a validated strategy for treating lung adenocarcinoma (LUAD) patients. One of the main challenges in ICIs treatment is the lack of efficient biomarkers for predicting response or resistance. Metabolic reprogramming has been proven to remodel the tumor microenvironment, altering the response to ICIs. We constructed a prognostic model as metabolism-related gene (MRG) of four genes by using weighted gene co-expression network analysis (WGCNA), the nonnegative matrix factorization (NMF), and Cox regression analysis of a LUAD dataset ( n = 500) from The Cancer Genome Atlas (TCGA), which was validated with three Gene Expression Omnibus (GEO) datasets ( n = 442, n = 226 and n = 127). The MRG was constructed based on BIRC5 , PLK1 , CDKN3 , and CYP4B1 genes. MRG-high patients had a worse survival probability than MRG-low patients. Furthermore, the MRG-high subgroup was more associated with cell cycle-related pathways; high infiltration of activated memory CD4 + T cells, M0 macrophages, and neutrophils; and showed better response to ICIs. Contrarily, the MRG-low subgroup was associated with fatty acid metabolism, high infiltration of dendric cells, and resting mast cells, and showed poor response to ICIs. MRG is a promising prognostic index for predicting survival and response to ICIs and other therapeutic agents in LUAD, which might provide insights on strategies with ICIs alone or combined with other agents.
Keyphrases
- end stage renal disease
- gene expression
- ejection fraction
- newly diagnosed
- cell cycle
- genome wide
- chronic kidney disease
- prognostic factors
- randomized controlled trial
- magnetic resonance imaging
- magnetic resonance
- dna methylation
- genome wide identification
- clinical trial
- patient reported outcomes
- wastewater treatment
- cell proliferation
- blood pressure
- signaling pathway
- heart rate variability
- oxidative stress
- endoplasmic reticulum stress
- induced apoptosis
- rna seq
- phase iii