Abstract
Objective A survival risk assessment model associated with a lung adenocarcinoma (LUAD) microenvironment was established and evaluated to identify effective independent prognostic factors for LUAD. Methods The public data were downloaded from the TCGA database, and ESTIMATE prediction software was used to score immune cells and stromal cells for tumor purity prediction. The samples were divided into the high-score group and the low-score group by the median value of the immune score (or stromal score). The Wilcoxon test was used for differential analysis. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) was performed using “clusterProfiler” of R package. Meanwhile, univariate and multivariate regression analysis was performed on DEGs to construct a multivariate Cox risk regression model with variable gene expression levels as independent prognostic factors affecting a tumor microenvironment (TME) and tumor immunity. Results This study found that LUAD patients with high immune cell (stromal cell) infiltration had better prognosis and were in earlier staging. Functional enrichment analysis revealed that most DEGs were related to the proliferation and activation of immune cells or stromal cells. A survival prediction model composed of 6 TME-related genes (CLEC17A, TAGAP, ABCC8, BCAN, FLT3, and CCR2) was established, and finally, the 6 feature genes closely related to the prognosis of LUAD were proved. The AUC value of the ROC curve in this model was 0.7, indicating that the model was reliable. Conclusion Six genes related to the LUAD microenvironment have a predictive prognostic value in LUAD.
Highlights
According to CA statistics in 2018, lung cancer is the most common cancer worldwide (11.6% of total cases) and the leading cause of cancer deaths (18.4% of total cancer deaths) [1], which seriously threatens human health
It was found that the scores of immune cells in tumor samples significantly varied in different clinical stages of lung adenocarcinoma (LUAD) and were decreased with the increasing of stage according to the clinical information of TCGA-LUAD (P < 0:05)
The infiltration degree of immune and stromal cells had a significant effect on the prognosis through survival analysis, which presented that the survival time of high infiltration patients was significantly longer than that of low infiltration patients (P < 0:05). (Figure 1(b))
Summary
According to CA statistics in 2018, lung cancer is the most common cancer worldwide (11.6% of total cases) and the leading cause of cancer deaths (18.4% of total cancer deaths) [1], which seriously threatens human health. Non-small-cell lung cancer (NSCLC) accounts for about 80% of lung cancer, which is further divided into three histological subtypes, including lung adenocarcinoma (LUAD), squamous cell carcinoma (LUSC), and large cell carcinoma (LCLC). The TME includes various cell types (endothelial cells, fibroblasts, immune cells, etc.) and extracellular components (cytokines, growth factors, hormones, extracellular matrix, etc.) that are surrounding tumor cells and nourished by a vascular network [3]. Immune cells (macrophages, mast cells, neutrophils, etc.) and adaptive immune cells (T and B lymphocytes) in the TME interact with tumor cells by direct contact or through chemokine and cytokine signal transduction, which influence tumor behavior and response to treatment. Many scholars have found that immune cells can both improve and obstruct therapeutic efficacy and may vary in their activation status and localization within the TME [3].
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