Establishment of the prognostic index of lung squamous cell carcinoma based on immunogenomic landscape analysis

Jianguo Zhang,Nannan Zhang,Junhong Zhang,Panpan Dai,Yangyi Li,Yan Gong,Jiangbo Ren,Jianzhong Zhang,Yuan Luo,Cheng Yuan,Conghua Xie,Wenjie Sun

doi:10.1186/s12935-020-01429-y

Abstract

BackgroundThe incidence of lung squamous cell carcinoma (LUSC) increased substantially in recent years. Systematical investigation of the immunogenomic pattern is critical to improve the prognosis of LUSC.MethodsBased on the TCGA and GEO dataset, we integrated the immune-related genes (IRGs) expression profile and the overall survival (OS) of 502 patients with LUSC. The survival-related and differentially-expressed IRGs in LUSC patients were evaluated by univariate cox regression and LASSO regression analysis. By applying multivariate cox analysis, a new prognostic indicator based on IRGs was established. We also used CIBERSORT algorithms and TIMER database to analyze immune infiltration of LUSC. Both gene set enrichment analysis (GSEA) and principal component analysis (PCA) was carried out for functional annotation. With the assist of computational biology, we also investigated the latent properties and molecular mechanisms of these LUSC-specific IRGs. We analyzed the correlation between immune checkpoints and risk score.ResultsA novel prognostic model was established based on 11 IRGS, including CXCL5, MMP12, PLAU, ELN, JUN, RNASE7, JAG1, SPP1, AGTR2, FGFR4, and TNFRSF18. This model performed well in the prognostic forecast, and was also related to the infiltration of immune cells. Besides, the high-risk groups and the low-risk groups exhibited distinct layout modes in PCA analysis, and GSEA results showed that different immune status among these groups.ConclusionsIn summary, our researches screened out clinically significant IRGs and proved the significance of IRG-based, individualized immune-related biomarkers in monitoring, prognosis, and discern of LUSC.

Highlights

The incidence of lung squamous cell carcinoma (LUSC) increased substantially in recent years
We found that 11 immune-related genes (IRGs) were significantly correlated with prognosis, and established a new independent prognostic model based on these genes
Identification of differentially expressed IRGs According to the list of IRGs from the Immunology database and analysis portal (ImmPort) database, 355 differentially expressed IRGs were identified, containing 135 upregulated and 220 downregulated (Fig. 1a, b)

Summary

Introduction

The incidence of lung squamous cell carcinoma (LUSC) increased substantially in recent years. CD4 + T cells were reported to recruit CD8 + T cells to the tumor site [16] and infect mucosa [17]. Several immune checkpoint inhibitors were found to enhance cytotoxic competence by targeting PD-1 ligand 1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), and programmed cell death protein 1 (PD-1). They had significant clinical effects on LUSC [20]. The prognostic value of IRGs was comprehensively explored to utilize personalized immune signals for optimal prognostic evaluations in non-squamous NSCLC patients [25]. The prognostic significance and clinical correlation of IRGs in LUSC remain to be explored

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Results

Conclusion