Dihydromyricetin Remodels the Tumor Immune Microenvironment in Hepatocellular Carcinoma: Development and Validation...

Dihydromyricetin (DHM), a natural dihydroflavonol, exhibits diverse pharmacological properties, including anti-inflammatory, antioxidant, and anti-tumor effects. However, its potential mechanism of action in the individualized therapy of hepatocellular carcinoma (HCC) remains unclear.

Potential therapeutic targets of DHM were identified using the Swiss Target Prediction database. The overlap between these targets and differentially expressed genes in HCC was analyzed to determine therapeutic targets. A prognostic model was constructed based on these genes, and patients were stratified into high- and low-risk groups. The associations between risk scores, clinical pathological characteristics, and overall survival were analyzed using Cox regression and Kaplan-Meier survival curves. The relationships between risk score and immune cell infiltration, immunosuppressive factors, and anticancer drug susceptibility were evaluated.

A three-gene prognostic model was established, comprising DTYMK, MAPT, and UCK2, designated as DHM-target genes (DHMGs). Patients in the high-risk group had significantly shorter overall survival than those in the low-risk group (p < 0.001; HR [95% CI] = 4.953 [2.544, 9.645]). Higher risk scores were correlated with more advanced tumor stages and grades. Comprehensive analysis of the tumor immune microenvironment revealed that high-risk patients exhibited significantly elevated TIDE scores, increased Treg cell infiltration, and markedly reduced stromal scores.

This study developed a prognostic model based on the potential target genes of DHM in HCC. This model effectively stratifies HCC patients, identifying a high-risk subgroup characterized by an immunosuppressive microenvironment. These findings provide a theoretical foundation for exploring DHM as a promising natural adjuvant for cancer immunotherapy.