Xiong Lecai, Wei Yanhong, Zhou Xiao, Dai Peng, Cai Yi, Zhou Xuefeng, Xu Ming, Zhao Jinping, Tang Hexiao
Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.
Department of Rheumatology and Immunology, Zhongnan Hospital, Wuhan University, Wuhan, 430071, People's Republic of China.
Cancer Manag Res. 2021 Nov 13;13:8535-8550. doi: 10.2147/CMAR.S335543. eCollection 2021.
The occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS.
We comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples.
We found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P<0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells.
AGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.
肺腺癌（LUAD）的发生发展与多种因素相关。多项研究表明，肾素-血管紧张素系统（RAS）在肺癌中起重要作用。本研究主要聚焦于RAS的重要组成部分——血管紧张素II受体1（AT1R）编码基因AGTR1。
我们基于从癌症基因组图谱（TCGA）获得的RNA测序数据，全面评估了AGTR1在泛癌中的表达。我们探讨了AGTR1与LUAD临床病理特征、预后及肿瘤微环境的相关性。我们还通过富集分析探索其机制，并在细胞系和组织样本中进行验证。
基于TCGA数据库，我们发现AGTR1在大多数肿瘤中表达较低且与预后相关。为进一步探究其机制，我们主要聚焦于LUAD。结合GEO数据库中的验证结果，AGTR1与LUAD较好的预后相关。AGTR1高表达与较少的淋巴结转移（P = 0.007）和MET突变（P = 0.019）相关。AGTR1高表达与抗肿瘤免疫微环境相关，B细胞、髓样树突状细胞、单核细胞浸润较高，而髓系来源的抑制细胞浸润较低（所有P < 0.05）。富集分析和体外验证结果表明，AGTR1可能通过PI3K/AKT3途径在LUAD中发挥作用。最后，我们通过组织样本和构建AGTR1过表达细胞验证了上述结果。
AGTR1通过PI3K/AKT3途径抑制肺腺癌的进展。
