Abstract
Background
G protein-coupled receptors (GPCRs) have been shown to have an important role in tumor development and metastasis, and abnormal expression of GPCRs is significantly associated with poor prognosis of tumor patients. In this study, we analyzed the GPCRs-related gene (GPRGs) and tumor microenvironment (TME) in skin cutaneous melanoma (SKCM) to construct a prognostic model to help SKCM patients obtain accurate clinical treatment strategies.
Methods
SKCM expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression analysis, LASSO algorithm, and univariate and multivariate cox regression analysis were used to screen prognosis-related genes (GPR19, GPR146, S1PR2, PTH1R, ADGRE5, CXCR3, GPR143, and OR2I1P) and multiple prognosis-good immune cells; the data set was analyzed according to above results and build up a GPR-TME classifier. The model was further subjected to immune infiltration, functional enrichment, tumor mutational load, immunotherapy prediction, and scRNA-seq data analysis. Finally, cellular experiments were conducted to validate the functionality of the key gene GPR19 in the model.
Results
The findings indicate that high expression of GPRGs is associated with a poor prognosis in patients with SKCM, highlighting the significant role of GPRGs and the tumor microenvironment (TME) in SKCM development. Notably, the group characterized by low GPR expression and a high TME exhibited the most favorable prognosis and immunotherapeutic efficacy. Furthermore, cellular assays demonstrated that knockdown of GPR19 significantly reduced the proliferation, migration, and invasive capabilities of melanoma cells in A375 and A2058 cell lines.
Conclusion
This study provides novel insights for the prognosis evaluation and treatment of melanoma, along with the identification of a new biomarker, GPR19.
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Data availability
All the data in our study can be accessed from the online databases. The R codes used during the current study are available on Jianguoyun (https://www.jianguoyun.com/p/DVAG3SAQjpbCCxjpvaAFIAA).
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This study was funded by the National Natural Science Foundation of China (82072182, 82002061).
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Conception and design: BiS, KW, and YP; data curation and methodology: YZ and ZC; YZ and BiS carried out the in vitro studies. Analysis and interpretation of data: YP; writing the manuscript: BiS; review of the manuscript: LC, ZY, and BaS; study supervision: ZY and BaS. All authors read and approved the final manuscript.
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Song, B., Wang, K., Peng, Y. et al. Combined signature of G protein-coupled receptors and tumor microenvironment provides a prognostic and therapeutic biomarker for skin cutaneous melanoma. J Cancer Res Clin Oncol 149, 18135–18160 (2023). https://doi.org/10.1007/s00432-023-05486-4
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DOI: https://doi.org/10.1007/s00432-023-05486-4