Background:Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma,
is a significant global health issue. Despite advancements in surgery and systemic therapies, drug resistance
remains a challenge, and more effective treatments are needed. Scutellarin, a natural flavonoid with
anticancer properties, is a promising therapeutic option for ccRCC.Methods:This present study identified the potential target genes of scutellarin by searching four databases
and utilized the TCGA-KIRC and GSE53757 datasets to identify ccRCC features genes. Protein-protein interaction
networks and molecular complex detection analyses determined the hub genes through which scutellarin
acts on ccRCC. Differential expression, receiver operating characteristic analysis, survival, and immune
cell infiltration analyses were conducted successively on these hub genes in tumor and normal tissues to verify
their clinical significance. The intracellular mechanism of the hub genes was explored using a single-cell dataset
(GSE222703) to elucidate the intracellular pathway through which scutellarin exerts its anti-ccRCC effects.
At last, molecular docking and molecular dynamics simulations were performed to confirm the stability
of the receptor protein of the hub gene binding to scutellarin.Results:158 scutellarin targets were collected and identified through database searches. Analyzing the
TCGA-KIRC and GSE53757 data separately identified finally 132 ccRCC feature genes through differential
expression analysis and WGCNA. Protein-protein interaction network and molecular complex detection analyses
revealed 26 hub genes potentially involved in hinge pathways of scutellarin in ccRCC. Differential expression
analysis revealed significant differences in the expression of these hub genes between tumor and
normal tissues. Receiver operating characteristic analysis demonstrated the fine diagnostic efficacy of these
hub genes. Survival analysis indicated that the hub genes TYMS and CDCA2 were associated with a better
prognosis, whereas the remaining hub genes had a poorer prognosis. Enrichment analysis revealed that hub
genes mainly involved oxidative stress and cell cycle regulation. Single-cell RNA sequencing analysis suggested
that most hub genes exert their effects on T helper cells. Molecular docking results showed stable
docking of hub genes with scutellari, except for SPAG5 and ASPM. Molecular dynamics simulations of the
most stable docking sites, KIF20A, TYMS, and KIF18B, indicated stable complex formation compared with
that of the internal reference protein GAPDH.Conclusion:This integrated study provides a comprehensive analysis of the molecular targets and pathways
affected by scutellarin in ccRCC. The identified hub genes and their related pathways present exciting prospects
for therapeutic intervention and highlight the potential of scutellarin as a novel treatment for ccRCC.
Additional research is necessary to investigate the precise molecular mechanisms and therapeutic advantages
of scutellarin in preclinical and clinical contexts.