Wu Fanqi, Zhang Longguo, Wang Li, Zhang Dekui
Department of Respiratory, Lanzhou University Second Hospital, Lanzhou, Gansu Province, People's Republic of China.
The Second Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, People's Republic of China.
Int J Gen Med. 2022 Feb 22;15:1865-1878. doi: 10.2147/IJGM.S351662. eCollection 2022.
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.
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.
AGT was overexpressed in GC tissues compared with normal gastric tissues (<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 <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.
AGT could act as a promising biomarker for prognosis and immune infiltration in GC.
血管紧张素原(AGT)作为肾素-血管紧张素系统(RAS)的一个组成部分,与胃癌(GC)的多种危险因素相关。然而,AGT与GC中肿瘤浸润淋巴细胞之间的关系仍不清楚。
基于癌症基因组图谱(TCGA)数据集分析AGT表达。采用Kaplan-Meier曲线评估AGT表达在胃癌患者预后中的作用。通过探索肿瘤免疫评估资源(TIMER)和基因表达谱交互式分析(GEPIA)进一步评估AGT表达与肿瘤免疫浸润之间的关联。我们还使用多个公共数据库分析AGT的异常甲基化,构建蛋白质-蛋白质相互作用(PPI)和基因本体(GO)分析。
与正常胃组织相比,AGT在GC组织中过表达(<0.05)。AGT高表达与GC患者较差的总生存期相关,尤其是在晚期GC患者中。免疫浸润分析显示,AGT与几种免疫细胞(包括B细胞、CD4+T细胞、巨噬细胞)相关,AGT表达还与自然杀伤细胞、肿瘤相关巨噬细胞、调节性T细胞等的标志物相关(均<0.05)。甲基化分析表明,低甲基化可能导致AGT异常上调。GO分析表明,AGT及其相关基因在激素调节的体循环动脉血压、肾素-血管紧张素调节的血容量、NIK/NF-κB信号传导、富含纤维胶凝蛋白-1的颗粒等方面富集。
AGT可能是GC预后和免疫浸润的一个有前景的生物标志物。