Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments
ABSTRACT 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 biomarker...
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Wiley
2025-05-01
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| Series: | The Clinical Respiratory Journal |
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| Online Access: | https://doi.org/10.1111/crj.70080 |
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| author | Feiyan Yang Jianye Yang Guobiao Yang Ya Zhang |
| author_facet | Feiyan Yang Jianye Yang Guobiao Yang Ya Zhang |
| author_sort | Feiyan Yang |
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| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-ab82a24063f64ea2ad5cc38a08ad4875 |
| institution | OA Journals |
| issn | 1752-6981 1752-699X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
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| series | The Clinical Respiratory Journal |
| spelling | doaj-art-ab82a24063f64ea2ad5cc38a08ad48752025-08-20T02:30:24ZengWileyThe Clinical Respiratory Journal1752-69811752-699X2025-05-01195n/an/a10.1111/crj.70080Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro ExperimentsFeiyan Yang0Jianye Yang1Guobiao Yang2Ya Zhang3Department of Respiratory and Critical Care Medicine Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital) Shaoxing ChinaDepartment of Respiratory and Critical Care Medicine Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital) Shaoxing ChinaDepartment of Respiratory and Critical Care Medicine Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital) Shaoxing ChinaDepartment of Respiratory and Critical Care Medicine Affiliated Hospital of Shaoxing University (The Shaoxing Municipal Hospital) Shaoxing ChinaABSTRACT 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.https://doi.org/10.1111/crj.70080G protein‐coupled receptorsimmune infiltrationlung adenocarcinomalung cancerprognosis |
| spellingShingle | Feiyan Yang Jianye Yang Guobiao Yang Ya Zhang Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments The Clinical Respiratory Journal G protein‐coupled receptors immune infiltration lung adenocarcinoma lung cancer prognosis |
| title | Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments |
| title_full | Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments |
| title_fullStr | Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments |
| title_full_unstemmed | Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments |
| title_short | Therapeutic and Prognostic Potential of G Protein‐Coupled Receptors in Lung Adenocarcinoma: Evidence From Transcriptome Data and In Vitro Experiments |
| title_sort | therapeutic and prognostic potential of g protein coupled receptors in lung adenocarcinoma evidence from transcriptome data and in vitro experiments |
| topic | G protein‐coupled receptors immune infiltration lung adenocarcinoma lung cancer prognosis |
| url | https://doi.org/10.1111/crj.70080 |
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