The role of Salvia miltiorrhiza compounds in hepatocellular carcinoma: a preliminary investigation based on computational analysis and liquid chromatography-tandem mass spectrometry

The potential therapeutic effect of Salvia miltiorrhiza on hepatocellular carcinoma (HCC) has been expounded. This study commenced to identify the diagnostic biomarkers and predict the role of Salvia miltiorrhiza in HCC. TCGA-LIHC cohort and HCCDB18 dataset were acquired. Chemical components of Salvia miltiorrhiza were identified. Differentially expressed genes (DEGs) were identified, and prognosis-associated DEGs were screened. The compound-gene network was established, and the biomarkers were identified accordingly. A nomogram was constructed and the diagnostic performance was assessed. Immune infiltration was evaluated via “CIBERSORT” and “estimate” packages. Pathways involved in biomarkers were analyzed by GSEA_4.2.2 software. Molecular docking model was constructed applying AutoDocktools software. The cell viability, migration and invasion of HCC cell line treated with β-Estradiol with/out overexpressing AKR1C3 were assessed. A total of 57 compounds were identified from Salvia miltiorrhiza and 54 risk and 4 protective prognostic DEGs were found in TCGA-LIHC cohort and HCCDB18 dataset. Further, we established a compound-gene network of 10 Salvia miltiorrhiza components and 3 prognostic DEGs. Accordingly, AURKB , HDAC11 and AKR1C3 were identified as the biomarkers to construct a nomogram, which displayed a strong diagnostic performance in HCC. Three biomarkers were notably correlated with most immune cells and were mainly involved in the pathways related to tumor proliferation, cell cycle, apoptosis and energy supply. Molecular docking model indicated that 3 compounds from Salvia miltiorrhiza (Ethinylestradiol, β-Estradiol, and 16alpha-Hydroxyestrone) could stably bind to AKR1C3 . Thereinto, β-Estradiol can inhibit the proliferation, migration and invasion of HCC cells by targeting AKR1C3 . This study provided a solid foundation for further exploring the pathogenesis of HCC as well as novel diagnostic biomarkers treatment targets, and potential management drugs for HCC.