Abstract
BackgroundLung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. In recent years, immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. However, the effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory.MethodsThe Cancer Genome Atlas (TCGA) LUAD dataset was downloaded. The differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2. The prognostic DEIGs were identified by COX regression. Protein-protein interaction (PPI) network was inferred by STRING using prognostic DEIGs with p value< 0.05. The prognostic model based on DEIGs was established using Lasso regression. Immunohistochemistry was used to assess the expression of FERMT2, FKBP3, SMAD9, GATA2, and ITIH4 in 30 cases of LUAD tissues.ResultsIn total,1654 DEIGs were identified, of which 436 genes were prognostic. Gene functional enrichment analysis indicated that the DEIGs were involved in inflammatory pathways. We constructed 4 models using DEIGs. Finally, model 4, which was constructed using the 436 DEIGs performed the best in prognostic predictions, the receiver operating characteristic curve (ROC) was 0.824 for 3 years, 0.838 for 5 years, 0.834 for 10 years. High levels of FERMT2, FKBP3 and low levels of SMAD9, GATA2, ITIH4 expression are related to the poor overall survival in LUAD (p < 0.05). The prognostic model based on DEIGs reflected infiltration by immune cells.ConclusionsIn our study, we built an optimal prognostic signature for LUAD using DEIGs and verified the expression of selected genes in LUAD. Our result suggests immune signature can be harnessed to obtain prognostic insights.
Highlights
Lung cancer is one of the most common diseases with the highest morbidity and mortality, in which the lung adenocarcinoma accounts for 40% of all cases
The differentially expressed gene analysis was performed by edgeR and DESeq2, and only differentially expressed immune genes (DEIGs) detected by both methods were included
The relationship between the expression of FERMT2, FKBP3, SMAD9, GATA2, IHIH4 and the overall survival of Lung adenocarcinoma (LUAD) In order to verify the clinical value of the model, we examined the expression of FERMT2, FKBP3, SMAD9, GATA2 and ITIH4 in 30 lung adenocarcinoma tissues by immunohistochemistry, considering the availability of antibodies. 86.67% (26/30) of LUAD patients tissue samples had positive expression of FERMT2, 83.33% (25/30) of FKBP3, 26.67% (8/30) of SMAD9, 23.33% (7/30) of GATA2 and 20.00% (6/30) of ITIH4 (Fig. 6)
Summary
Lung cancer is one of the most common diseases with the highest morbidity and mortality, in which the lung adenocarcinoma accounts for 40% of all cases. The morbidity and mortality of lung adenocarcinoma have gradually increased [1]. Chemotherapy, radiotherapy and targeted therapy are the most common. Increasing evidence suggested that tumor microenvironment (TME) which is composed of tumor cells, immune cells, stromal cells, inflammatory mediators and extracellular matrix [2], taking part in the tumor progression and drug resistance [3, 4]. Immune cells and inflammatory mediators have been proved to be valuable for the prognostic of LUAD [5]. Lung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. Immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. The effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory
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