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Therapeutic and Prognostic Potential of G Protein-Coupled Receptors in Lung Adenocarcinoma: Evidence From
Feiyan Yang1, Jianye Yang1, Guobiao Yang1
1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital), Shaoxing, China.
Background:
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).
Methods:
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.
Results:
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.
Conclusion:
GPCRs demonstrated prognostic potential in LUAD, with five genes identified as potential therapeutic targets and prognostic biomarkers for LUAD.
Insights
G protein-coupled receptors (GPCRs) show prognostic potential in lung adenocarcinoma (LUAD). Five GPCRs (OR51E1, LGR4, ADRB1, ADGRD1, ADGRE3) were identified as potential therapeutic targets and biomarkers for LUAD patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- G protein-coupled receptors (GPCRs) are crucial in cell signaling and increasingly recognized as cancer drivers.
- Their role in lung adenocarcinoma (LUAD) as therapeutic targets or biomarkers remains underexplored.
Purpose of the Study:
- To investigate the prognostic value of GPCRs in LUAD.
- To identify potential GPCR-based biomarkers and therapeutic targets for LUAD.
Main Methods:
- Analyzed LUAD expression profiles and clinical data from TCGA datasets (GSE30219, GSE18842).
- Employed weighted gene co-expression network analysis (WGCNA) to identify LUAD-associated modules.
- Utilized univariate Cox, LASSO, and multivariate Cox regression for prognostic signature identification.
- Assessed immune cell infiltration and drug sensitivity, with in vitro validation for OR51E1.
Main Results:
- Identified 38 dysregulated GPCRs in LUAD, with patients showing lower GPCR scores.
- Developed a five-gene prognostic signature (OR51E1, LGR4, ADRB1, ADGRD1, ADGRE3) with moderate predictive power for LUAD survival.
- Risk score correlated with immune cell infiltration patterns and positively associated with sensitivity to cisplatin, ribociclib, and pevonedistat.
- Silencing OR51E1 inhibited LUAD cell malignancy.
Conclusions:
- GPCRs hold significant prognostic potential in lung adenocarcinoma.
- Five specific GPCRs (OR51E1, LGR4, ADRB1, ADGRD1, ADGRE3) are proposed as promising therapeutic targets and prognostic biomarkers for LUAD.
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