Background:
Lung adenocarcinoma (LUAD) is one of the most common malignant
cancers. Neutrophil extracellular traps (NETs) have been discovered to play a crucial role in the
pathogenesis of LUAD. We aimed to establish an innovative prognostic model for LUAD
based on the distinct expression patterns of NETs-related genes.
background:
Neutrophil extracellular traps (NETs) plays dual roles in lung adenocarcinoma (LUAD). We aimed to develop a novel prognostic model for LUAD based on the distinct expression patterns of NETs-related genes.
Methods:
The TCGA LUAD dataset was utilized as the training set, while GSE31210,
GSE37745, and GSE50081 were undertaken as the verification sets. The patients were grouped
into clusters based on the expression signature of NETs-related genes. Differentially expressed
genes between clusters were identified through the utilization of the random forest and LASSO
algorithms. The NETs score model for LUAD prognosis was developed by multiplying the expression
levels of specific genes with their corresponding LASSO coefficients and then summing
them. The validity of the model was confirmed by analysis of the survival curves and
ROC curves. Additionally, immune infiltration, GSEA, mutation analysis, and drug analysis
were conducted. Silencing ABCC2 in A549 cells was achieved to investigate its effect.
Results:
We identified six novel NETs-related genes, namely UPK1B, SFTA3, GGTLC1,
SCGB3A1, ABCC2, and NTS, and developed a NETs score signature, which exhibited a significant
correlation with the clinicopathological and immune traits of the LUAD patients. High-risk
patients showed inhibition of immune-related processes. Mutation patterns exhibited variability
among the different groups. AZD3759, lapatinib, and dasatinib have been identified as potential
candidates for LUAD treatment. Moreover, the downregulation of ABCC2 resulted in the induction
of apoptosis and suppression of migration and invasion in A549 cells.
Conclusion:
Altogether, this study has identified a novel NET-score signature based on six
novel NET-related genes to predict the prognosis of LUAD and ABCC2 and has also explored
a new method for personalized chemo-/immuno-therapy of LUAD.
