Abstract
BackgroundGastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown.MethodsThe ATAC-seq was used to identify genes with chromatin accessibilities in promoter regions. The RNA-seq datasets were performed to identify differentially expressed genes (DEGs). Pearson correlation analysis with the mRNA expression of three families of tumor-related inflammation TFs was used to filter downstream DEGs. Cox univariate survival analysis was performed to identify the prognostic value. The ImmPort database and CIBERSORTx algorithm were used to investigate the regulatory relationship between hub DEGs and immune cells. Immunohistochemistry (IHC) and multidimensional database were performed to verification.ResultsIn this case, we require 2,454 genes with chromatin accessibility in promoter regions by ATAC-seq. Based on the gene expression profiles (RNA-seq), we identified 365 genes with chromatin accessibility and differential expression. Combined with the Cox univariate survival analysis, we identified 32 survival-related DEGs with chromatin accessibility. According to ImmPort database, CXCL3, PLXNC1, and EDN2 were identified as immune- related genes in STAD. By applying the CIBERSORTx algorithm and Pearson correlation, PLXNC1 was the only gene correlated with various immune cells, significantly associated with M2 macrophages. Furthermore, gene set variation analysis (GSVA) suggests the “hallmark_interferon_gamma_response” pathway was most significantly correlated with PLXNC1. Immunohistochemistry results revealed that PLXNC1 protein level was significantly higher in STAD tissues than in normal tissues (p < 0.001).ConclusionPLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma.
Highlights
Gastric cancer (GC), the third leading cause of malignancyrelated deaths, remains a considerable health problem worldwide (Siegel et al, 2019)
Gene set variation analysis (GSVA) suggests the “hallmark_interferon_gamma_response” pathway was most significantly correlated with PLXNC1
PLXNC1, regulated by IRF5, is an immune-related gene that was significantly associated with M2 macrophages and poor outcome in stomach adenocarcinoma
Summary
Gastric cancer (GC), the third leading cause of malignancyrelated deaths, remains a considerable health problem worldwide (Siegel et al, 2019). There have been great advances in diagnostic technology and therapeutic methods in recent decades, the prognosis of STAD patients remains poor. Much attention has been paid to the inflammatory response during initiation, promotion, and progression of GC (Mantovani et al, 2008; Bernard et al, 2019). Regarded as a model of inflammation-related cancer, the tumor immune microenvironment plays a vital role in tumor progression, especially tumor-associated macrophages (Li et al, 2019). Accumulating evidence indicates that a high rate of macrophage infiltration is strongly associated with poor prognosis of STAD (Su et al, 2018). Gastric cancer is associated with tumor microenvironment and chronic inflammation, but the underlying tumor-promoting mechanisms still remain unknown
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