Clinical applicability of renin-angiotensin system inhibitors in cancer treatment

Abstract

The renin-angiotensin system (RAS) regulates physiological functions of the cardiovascular system, kidneys, and other tissues. Various in vivo and in vitro studies have shown that RAS plays a pivotal role in the development of malignant tumors, while several retrospective studies have confirmed that patients undergoing long-term RAS inhibitors (RASi) treatment have a lowered risk of cancer. Moreover, blocking RAS has been shown to inhibit tumor growth, metastasis, and angiogenesis in various experimental models of malignant tumors. Herein, we review the available RASi-related literature and provide an analysis using the scientific atlas software VOSviewer. We observed that recent studies have primarily focused on gene expression, tumor biology, and survival analysis. Through an in-depth data analysis from the Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx), we identified the impact of AGTR1, an essential component of RAS, on tumors, and we discuss the underlying biological mechanism of RASi. Furthermore, we outline the research progress and potential use of RASi in tumor treatment. Overall, RASi may be a promising adjunct in cancer therapy.

Keywords: AGTR1; RAS inhibitors; Renin-angiotensin system; angiotensin receptor blockers; tumor.

Figure 1

Gene expression profile of AGTR1 in 33 cancer types and matched non-tumor samples. Each point represents a different tumor or normal sample. Short black lines represent the median gene expression level. The data were obtained through Gene Expression Profiling Interactive Analysis (GEPIA). T: tumor tissue; N: normal tissue; n: number; ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B-cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukemia; LGG: brain lower grade glioma; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma.

Figure 2

A. Bibliometric map of RASi application during year 2000 to 2020. B. Bibliometric map of the application of RASi and tumor from 2000 to 2020. Dot size is proportional to the frequencies of particular keywords in analyzed articles. Lines between two dots indicate that these two keywords appear in the same article. The thicker the line, the more frequently the two keywords appear in the same article. The color indicates the year when a keyword appears most often in an article.

Figure 3

The effect of high expression of AGTR1 in tumor tissue on the survival of patients. The median expression level of AGTR1 was divided into one-to-one groups. A. Bladder urothelial carcinoma (BLCA); B. Colon adenocarcinoma (COAD); C. Rectal adenocarcinoma (READ); D. Skin cutaneous melanoma (SKCM); E. Uterine corpus endometrial carcinoma (UCEC); F. Glioblastoma multiforme (GBM); G. Brain lower-grade glioma (LGG); H. Pancreatic adenocarcinoma (PAAD); I. Kidney renal clear cell carcinoma (KIRC); J. Thymoma (THYM). The data was obtained through Gene Expression Profiling Interactive Analysis (GEPIA).