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Analysis of inflammatory macrophage-related molecular patterns and immune microenvironment in esophageal cancer

bioinformatics
cell-biology
immunology
oncology

Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy with a poor prognosis. Moreover, the mechanism underlying tumor immunosuppression remains unclear due to the complexity and heterogeneity of tumors. Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment (TME).

Objective

To gain deeper insights into the interactions between macrophage-related genes (MRGs), inflammation-related genes (IRGs), and ESCC-related genes in ESCC.

Methods

We downloaded inflammation-related genes (IRGs) from the MSigDB database and differentially expressed genes (DEGs) between ESCC and normal from TCGA. We retained 260 overlapping genes from IRGs and ESCC-related genes as IRGs-DEGs for subsequent analysis. Weighted gene co-expression network analysis (WGCNA) was used to identify macrophage-related genes (MRGs) in the ESCC patient population. The 116 overlapping genes between IRGs-DEGs and MRGs were defined as DEIRG-MRGs. Gene Set Variation Analysis (GSVA) was used to calculate the DEIRG-MRGs enrichment score. Based on the DEIRG-MRGs enrichment score, ECSS patients were divided into high and low groups. And then we explored the difference between the immune microenvironment, immunotherapy efficiency, and drug sensitivity in two groups.

Results

Compared to the low DEIRG-MRG score group, the prognosis of the high DEIRG-MRG score group was poorer. Drug sensitivity was significantly different between the high DEIRG-MRG score group and the low DEIRG-MRG score group.

Conclusions

Hub genes (SPI1, TYROBP, FCGR1A, CXCL9, and ITGB2) related to ESCC, inflammation, and macrophages were identified and validated using patient samples. Our immune-related genes provide reliable value in evaluating microenvironmental characteristics, therapeutic sensitivity of ESCC, and new insights into ESCC precise therapy.

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