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. 2022 Feb 22:15:1865-1878.
doi: 10.2147/IJGM.S351662. eCollection 2022.

AGT May Serve as a Prognostic Biomarker and Correlated with Immune Infiltration in Gastric Cancer

Fanqi Wu #  1 , Longguo Zhang #  2 , Li Wang #  3 , Dekui Zhang  4
Affiliations

AGT May Serve as a Prognostic Biomarker and Correlated with Immune Infiltration in Gastric Cancer

Fanqi Wu et al. Int J Gen Med. .

Abstract

Purpose: Angiotensinogen (AGT), as a component of the renin-angiotensin system (RAS), is associated with multiple risk factors for gastric cancer (GC). However, the relationship between AGT and tumor-infiltrating lymphocytes in GC remains elusive.

Methods: AGT expression was analyzed based on the Cancer Genome Atlas (TCGA) dataset. Kaplan-Meier curve was employed to assess the role of AGT expression in gastric patients' prognosis. The association between AGT expression and tumor immune infiltration was further evaluated via exploring Tumour Immune Estimation Resource (TIMER) and The Gene Expression Profiling Interactive Analysis (GEPIA). We also used multiple public databases to analyse the aberrant methylation of AGT, construct protein-protein interaction (PPI) and gene ontology (GO) analyses.

Results: AGT was overexpressed in GC tissues compared with normal gastric tissues (P<0.05). High AGT expression related with poorer overall survival of patients with GC, especially in advanced GC patients. Immune infiltration analysis revealed that AGT was associated with several immune cells (including B cells, CD4+ T cells, macrophages), and AGT expression was also associated with the markers of NK cells, TAMs, Tregs, and so on (all P<0.05). Methylation analysis indicated that hypomethylation may lead to abnormal upregulation of the AGT. GO analysis showed that AGT and its related genes were enriched in systemic arterial blood pressure by hormone, regulation of blood volume by renin-angiotensin, NIK/NF-kappaB signaling, ficolin-1-rich granule and so on.

Conclusion: AGT could act as a promising biomarker for prognosis and immune infiltration in GC.

Keywords: angiotensinogen; methylation; prognosis; stomach adenocarcinoma; tumor-infiltrating.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
AGT expression in GC tissues and normal tissues based on TCGA database (A) and GEPIA database (B). The diagnostic value of AGT in GC using ROC curve (C). Correlation between AGT expression level and OS (D) and RFS/DFS (E) in GC based on TCGA dataset. Correlation between AGT expression and OS in GC based on GEPIA database (F), Kaplan-Meier Plotter (G); Correlation between AGT expression and RFS/DFS based on GEPIA database (H), Kaplan-Meier Plotter (I).
Figure 2
Figure 2
(A) The relationship between AGT gene copy number alterations and immune cell infiltration levels. (B) Prognostic value of immune cells and AGT in GC. (C) Correlation of AGT expression with immune infiltration level in GC.
Figure 3
Figure 3
Immune cell markers associated with AGT (P<0.01), including (A) Dendritic cell; (B) Th17 cell; (C) NK cell; (D) CD4+ T cell; (E) Th2 cell; (F) B cell; (G) Neutrophil; (H) TAM; (I) Monocyte; (J) M2 macrophage; (K) Treg; (L) Th1 cell.
Figure 4
Figure 4
Methylation analysis of AGT. (A) Correlation between AGT mRNA expression and AGT DNA methylation. (B) AGT methylation between GC tissues and normal tissues. (C) Different methylated sites associated with AGT. The relationship between CpG sites and GC prognosis, including (D) cg07502417; (E) cg24474852; (F) cg22647018; (G) cg26882410; (H) cg14523948; (I) cg27401395.
Figure 5
Figure 5
PPI network construction based on STRING database (A) and GeneMANIA database (B). GO analysis results (C).
See this image and copyright information in PMC

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