Evaluation of Therapeutic Mechanism of Hedyotis Diffusa Willd (HDW)‒ Scutellaria Barbata (SB) in Clear Cell Renal Cell Carcinoma Singlecell RNA Sequencing and Network Pharmacology.

OBJECTIVE

The present study aimed to investigate the therapeutic mechanism of Hedyotis diffusa Willd (HDW) and Scutellaria barbata (SB) in ccRCC using a combination of single-cell RNA sequencing (scRNA-seq) and network pharmacology.

METHODS

The active ingredients and potential molecular targets of HDW-SB were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. Gene expression data (GSE53757) were obtained from the Gene Expression Omnibus database. The hub genes of HDW-SB against ccRCC were identified via the protein-protein interaction network, and further analyzed by molecular complex detection. The roles of these genes in the diagnosis and immune infiltration of ccRCC were analyzed. The clinical significance of hub genes was verified using scRNA-seq data (GSE121638) and molecular docking.

RESULTS

Following the PPI network analysis, 29 hub genes of HDW-SB against ccRCC were identified. All hub genes, except for , had significantly different expressions in tumor tissue and a more accurate diagnosis of ccRCC. Fifteen cell clusters were defined based on the scRNA-seq dataset, and the clusters were annotated as six cell types using marker genes. and from hub genes were highly expressed in NK cells. Three active compounds, quercetin, luteolin, and baicalein, were found to target and from the compound-target interaction network.

CONCLUSION

29 hub genes of HDW-SB against ccRCC were identified and showed good performance in terms of diagnosis and prognosis. Moreover, among these hub genes docking with the main ingredients of HDW-SB, and exerted anti-ccRCC effects through NK cells.