Yang Feiyan, Yang Jianye, Yang Guobiao, Zhang Ya
Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital), Shaoxing, China.
Clin Respir J. 2025 May;19(5):e70080. doi: 10.1111/crj.70080.
G protein-coupled receptors (GPCRs), the largest family of cell-surface molecules involve in various signal transduction, have recently been recognized as important drivers of cancer. However, few studies have reported on the potential of GPCRs as therapeutic targets or biomarkers in lung adenocarcinoma (LUAD).
The expression profiles and clinical data of LUAD in the GSE30219 and GSE18842 datasets of the Cancer Genome Atlas were analyzed. LUAD-associated module genes were screened utilizing weighted gene co-expression network analysis (WGCNA). Prognostic signature genes were identified by univariate Cox survival analysis, LASSO regression, and multivariate Cox regression analyses. The immune status was evaluated and drug sensitivity was determined, conducting in vitro experiments for validation.
Patients with LUAD exhibited lower GPCR score than the controls, and 38 dysregulated GPCRs were identified by screening with differential analysis and WGCNA module genes. An optimal prognostic signature was identified, including OR51E1, LGR4, ADRB1, ADGRD1, and ADGRE3. The model established based on these five genes harbored moderate predictive performance for the survival of patients with LUAD. The risk score was negatively correlated with the infiltrating levels of multiple immune cells, including M2 macrophages, myeloid dendritic cells, and neutrophils, but positively correlated with fewer immune cells, such as Th1/Th2 CD4 + T cell. ADGRE3 and OR51E1 expression was positively correlated with drug sensitivity, including to cisplatin, ribociclib, and pevonedistat. Silencing OR51E1 inhibited the malignant cytological behaviors of LUAD cells.
GPCRs demonstrated prognostic potential in LUAD, with five genes identified as potential therapeutic targets and prognostic biomarkers for LUAD.
G蛋白偶联受体（GPCRs）是参与各种信号转导的最大细胞表面分子家族，最近被认为是癌症的重要驱动因素。然而，关于GPCRs作为肺腺癌（LUAD）治疗靶点或生物标志物的潜力的研究报道较少。
分析癌症基因组图谱中GSE30219和GSE18842数据集中LUAD的表达谱和临床数据。利用加权基因共表达网络分析（WGCNA）筛选LUAD相关模块基因。通过单变量Cox生存分析、LASSO回归和多变量Cox回归分析确定预后特征基因。评估免疫状态并确定药物敏感性，进行体外实验验证。
LUAD患者的GPCR评分低于对照组，通过差异分析和WGCNA模块基因筛选鉴定出38个失调的GPCR。确定了一个最佳预后特征，包括OR51E1、LGR4、ADRB1、ADGRD1和ADGRE3。基于这五个基因建立的模型对LUAD患者的生存具有中等预测性能。风险评分与多种免疫细胞的浸润水平呈负相关，包括M2巨噬细胞、髓样树突状细胞和中性粒细胞，但与较少的免疫细胞呈正相关，如Th1/Th2 CD4 + T细胞。ADGRE3和OR51E1的表达与药物敏感性呈正相关，包括对顺铂、瑞博西尼和pevonedistat的敏感性。沉默OR51E1可抑制LUAD细胞的恶性细胞学行为。
GPCRs在LUAD中显示出预后潜力，有五个基因被确定为LUAD的潜在治疗靶点和预后生物标志物。
