背景:粘附G蛋白偶联受体(aGPCRs),G蛋白偶联受体(GPCR)超家族的一个独特子集,在各种生理和病理过程中发挥关键作用,与肿瘤发展有关。尽管乳腺癌(BRCA)在全球范围内流行,作为潜在药物靶标或生物标志物的特异性aGPCRs仍未充分开发。
方法:UALCAN,GEPIA,Kaplan-Meier绘图仪,MethSurv,cBiopportal,字符串,遗传狂躁症,大卫,定时器,Metascape,在这项工作中应用了qPCR。
结果:我们的分析显示,BRCA原发肿瘤中ADGRB2、ADGRC1、ADGRC2、ADGRC3、ADGRE1、ADGRF2、ADGRF4和GRADL1的转录水平显著升高。进一步分析表明,某些aGPCRs的表达与BRCA的病理分期之间存在显着相关性。ADGRA1,ADGRF2,ADGRF4,ADGRG1,ADGRG2,ADGRG4,ADGRG6和ADGRG7的高表达与BRCA患者的不良总生存期(OS)显着相关。此外,ADGRF2和ADGRF4的高表达表明BRCA患者的无复发生存率(RFS)较差.RT-qPCR实验还证实在BRCA细胞和组织中ADGRF2和ADGRF4的mRNA水平较高。功能分析强调了aGPCR的不同作用,包括GPCR信号和代谢能量储备。此外,aGPCRs可通过其对免疫状态的影响而影响或积极参与BRCA的发展。
结论:aGPCRs,特别是ADGRF2和ADGRF4,有望作为BRCA的免疫治疗靶点和预后生物标志物。
BACKGROUND: Adhesion G protein-coupled receptors (aGPCRs), a distinctive subset of the G protein-coupled receptor (GPCR) superfamily, play crucial roles in various physiological and pathological processes, with implications in tumor development. Despite the global prevalence of breast cancer (
BRCA), specific aGPCRs as potential drug targets or biomarkers remain underexplored.
METHODS: UALCAN, GEPIA, Kaplan-Meier Plotter, MethSurv, cBiopportal, String, GeneMANIA, DAVID, Timer, Metascape, and qPCR were applied in this work.
RESULTS: Our analysis revealed significantly increased transcriptional levels of ADGRB2, ADGRC1, ADGRC2, ADGRC3, ADGRE1, ADGRF2, ADGRF4, and ADGRL1 in
BRCA primary tumors. Further analysis indicated a significant correlation between the expressions of certain aGPCRs and the pathological stage of BRCA. High expression of ADGRA1, ADGRF2, ADGRF4, ADGRG1, ADGRG2, ADGRG4, ADGRG6, and ADGRG7 was significantly correlated with poor overall survival (OS) in
BRCA patients. Additionally, high expression of ADGRF2 and ADGRF4 indicated inferior recurrence-free survival (RFS) in BRCA patients. The RT-qPCR experiments also confirmed that the mRNA levels of ADGRF2 and ADGRF4 were higher in
BRCA cells and tissues. Functional analysis highlighted the diverse roles of aGPCRs, encompassing GPCR signaling and metabolic energy reserves. Moreover, aGPCRs may exert influence or actively participate in the development of
BRCA through their impact on immune status.
CONCLUSIONS: aGPCRs, particularly ADGRF2 and ADGRF4, hold promise as immunotherapeutic targets and prognostic biomarkers in BRCA.