Pan-cancer analysis of the angiotensin II receptor-associated protein as a prognostic and immunological gene predicting immunotherapy responses in pan-cancer

Abstract

Background: Understanding interior molecular mechanisms of tumorigenesis and cancer progression contributes to antitumor treatments. The angiotensin II receptor-associated protein (AGTRAP) has been confirmed to be related with metabolic products in metabolic diseases and can drive the progression of hepatocellular carcinoma and colon carcinoma. However, functions of AGTRAP in other kinds of cancers are unclear, and a pan-cancer analysis of AGTRAP has not been carried out.Methods and materials: We downloaded data from The Cancer Genome Atlas and Genotype-Tissue Expression dataset and The Human Protein Atlas databases and then used R software (version 4.1.1) and several bioinformatic tools to conduct the analysis.Results: In our study, we evaluated the expression of AGTRAP in cancers, such as high expression in breast cancer, lung adenocarcinoma, and glioma and low expression in kidney chromophobe. Furthermore, our study revealed that high expression of AGTRAP is significantly related with poor prognosis in glioma, liver cancer, kidney chromophobe, and so on. We also explored the putative functional mechanisms of AGTRAP across pan-cancer, such as endoplasmic reticulum pathway, endocytosis pathway, and JAK-STAT signaling pathway. In addition, the connection between AGTRAP and tumor microenvironment, tumor mutation burden, and immune-related genes was proven.Conclusion: Our study provided comprehensive evidence of the roles of AGTRAP in different kinds of cancers and supported the relationship of AGTRAP and tumorous immunity.

The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis

“…For AGTRAP, we found a significantly higher expression of this marker in GBM compared to the adjacent non-malign brain parenchyma. These results are in line with a recent study by Hong et al, demonstrating that AGTRAP was overexpressed at both mRNA levels (TCGA+GTEx database) and protein levels (CPTAC database) in many tumours, including GBM [8]. Our study further showed that GBM patients with high levels of AGTRAP had a significantly shorter OS and PFS than patients with low levels of this marker.…”

“…Indeed, previous studies linked AGTRAP with the activation of wellestablished tumourigenic pathways such as MAPK and AKT/mTOR [6,7]. Furthermore, very recent studies found a direct correlation between AGTRAP levels and the numbers of tumour-infiltrating M2 macrophages in GBM [8]. Since M2 macrophages can drive tumour progression through immunosuppression in gliomas [42], it would be interesting for future studies to elucidate the exact involvement of AGTRAP in this context.…”

“…AGTRAP (Angiotensin II Type I Receptor-associated Protein) is a member of the renin-angiotensin system, which specifically interacts with the AT1 receptor to regulate cardiovascular and fluid homeostasis [5]. In cancer, AGTRAP can promote tumour progression through activation of the MAPK and AKT/mTOR signaling pathways [6,7], but potentially also through regulation of immunological processes, such as T-cell exhaustion or recruitment of pro-inflammatory and immunosuppressive immune cells [6,8]. ALKBH3 (AlkB Homolog 3)/PCA-1 (Prostate Cancer Antigen-1) is a DNA/RNA repair enzyme, which acts as a demethylase to regulate cellular metabolism (reviewed in [9]).…”