粘附G蛋白偶联受体G2(ADGRG2)是一种孤儿粘附G蛋白偶联受体(GPCR),在某些癌症中具有促进肿瘤的作用;然而,尚未在肝细胞癌(HCC)中进行系统研究。在目前的研究中,我们利用多个数据库分析了ADGRG2在HCC中的表达,诊断和预后价值及其与免疫浸润和炎症因子的相关性。通过qPCR验证ADGRG2的功能和上游调控miRNA,蛋白质印迹,CCK8,伤口愈合,和双荧光素酶测定。结果表明,ADGRG2在HCC中明显较高,生存率较差,尤其是AFP≤400ng/mL亚组。功能富集分析表明,ADGRG2可能参与癌症通路和免疫相关通路。体外,siRNA介导的ADGRG2沉默可以抑制Huh7和HepG2细胞的增殖和迁移。ADGRG2与中性粒细胞呈极显著正相关。此外,NET相关基因被过滤和确认,例如ENO1和S100A9。同时,ADGRG2的高表达也伴随着数量最多的炎性细胞因子,趋化因子,和趋化因子受体和良好的免疫治疗效果。最后,AGDGR2可能对两种药物(PIK-93和NPK76-II-72-1)敏感,可被miR-326靶向。总之,ADGRG2可能作为HCC诊断的新生物标志物和药物靶点,免疫疗法,中性粒细胞和炎症过程与肝癌的发生发展有关。
Adhesion G protein-coupled receptor G2 (
ADGRG2) is an orphan adhesion G protein-coupled receptor (GPCR), which performs a tumor-promoting role in certain cancers; however, it has not been systematically investigated in hepatocellular carcinoma (HCC). In the current study, we utilized multiple databases to analyze the expression and diagnostic and prognostic value of ADGRG2 in HCC and its correlation with immune infiltration and inflammatory factors. The function and upstream regulatory miRNA of
ADGRG2 were validated through qPCR, Western blot, CCK8, wound healing, and dual luciferase assays. It turned out that
ADGRG2 was significantly higher in HCC and had a poor survival rate, especially in AFP ≤ 400 ng/mL subgroups. Functional enrichment analysis suggested that ADGRG2 may be involved in cancer pathways and immune-related pathways. In vitro, siRNA-mediated ADGRG2 silencing could inhibit the proliferation and migration of Huh7 and HepG2 cells. There was a highly significant positive correlation between
ADGRG2 and neutrophils. Moreover, NET-related genes were filtered and confirmed, such as ENO1 and S100A9. Meanwhile, the high expression of ADGRG2 was also accompanied by the highest number of inflammatory cytokines, chemokines, and chemokine receptors and good immunotherapy efficacy. Finally, AGDGR2 may be sensitive to two drugs (PIK-93 and NPK76-II-72-1) and can be targeted by miR-326. In conclusion,
ADGRG2 may serve as a novel biomarker and drug target for HCC diagnosis, immunotherapy, and prognosis and was related to neutrophils and the inflammatory process of liver cancer development.