## 4 Discussion  
This study provided a comprehensive computational analysis of ADGRG3 as a target in cancer and immune pathways, highlighting its differential expression across various cancers and its role in immune cell interactions. This study's findings indicate elevated ADGRG3 expression in cancers such as AML, CHOL, and HNSC, suggesting an active role of ADGRG3 in tumor progression and immune-related pathways. The specificity of the high ADGRG3 expression in AML subtypes M2, M6, M7, and M4 points to its potential role in hematological malignancies, where ADGRG3 may influence inflammatory and immune pathways involved in cancer progression. A previous study highlighted ADGRG3 as a key adhesion GPCR in AML, associating its high expression-alongside that of ADGRE2 and other GPCRs--with poor clinical outcomes, reduced overall survival, and inflammation [17]. Strengthening this link, a recent in vitro and in vivo study reported ADGRE2's role in AML by promoting leukemic stem cell survival and tumor progression via the MEK/AP1/DUSPI axis. ADGRE2 knockdown impaired proliferation, induced apoptosis, and reduced LSC frequency, while xenograft models showed delayed leukemia progression and prolonged survival. Given the structural and functional similarities among adhesion GPCRs, this evidence highlights ADGRG3's potential role in AML and supports the need for further experimental validation [23]. To increase the overall precision and specificity of the experimental results, in silico investigations were employed. The interaction between the targeted ginseng and the ADGRG3 biomolecule is better understood through the use of computational methods, such as physiological and ADMET characteristics and MD. Additionally, these techniques facilitate the prediction of possible toxicological and pharmacokinetic characteristics. In contrast to conventional methods, in silico projections for drug similarity, chemical descriptors, and ADMET characteristics help identify new lead compounds more quickly [70]. The MD technique has been employed to predict powerful therapeutic compounds that inhibit the proliferation of cancer stem cells [71]. MD results can help advance potential drug design strategies [72]. Computer-based drug design tools can help reduce costs and accelerate drug discovery processes, with molecular dynamics serving as a final filter following docking and optimizing hits (or leads) [73]. In the current study, the virtual screening identified five top ginseng--Rg3, Rk3, F5, Rg7, and F1--as promising ADGRG3 ligands, with Rg3 showing the strongest binding affinity. Rg3 has been emphasized for its anticancer effects, including inhibition of tumor growth, angiogenesis, and metastasis, while Rk3 has shown significant activity against non-small cell lung cancer through apoptosis induction and cell cycle arrest. Additionally, F5, Rg7, and F1 are known to regulate cancer cell metabolism, targeting pathways essential for tumor survival [74; 75; 76]. The strong binding of Rg3 and Rk3 to ADGRG3 suggests a probable dual role in modulating immune- and cancer-related pathways, which warrants further experimental validation. These ginseng bind with ADGRG3's key binding pocket residues through hydrogen bonds and hydrophobic contacts. Studies have shown the efficient absorption and metabolism of ginseng such as Rg3 and Rk3, with Rg3 undergoing significant biotransformation and Rk3 targeting the PI3K/AKT pathway to regulate autophagy and apoptosis. Ginsenoside F1, while showing low brain permeability, can achieve enhanced delivery via intranasal administration with absorption enhancers. The gene expression analysis of reported TCGA revealed that ADGRG3 is upregulated in several cancers, with the highest increase observed in AML. Supporting these findings, previous studies demonstrated that red ginseng extract, rich in ginsengides Rg3, F5, Rg7, F1, and Rk3, exerts significant anticancer activity against leukemia cells by inducing apoptosis, suppressing proliferation, and inhibiting extramedullary infiltrration [77; 78; 79].