肝细胞癌中 HDACs 预后意义及生物学功能的综合分析

Background: The prognostic significance and biological functions of the histone deacetylases (HDACs) gene family in liver hepatocellular carcinoma (LIHC) have not been fully investigated. Methods: Using Kaplan-Meier and Cox regression analysis, this study determined if HDAC genes were relevant for prognosis in LIHC.

A regression model utilizing HDAC genes and the least absolute shrinkage and selection operator (LASSO) was created to foretell LIHC risk. A selective inhibitor of endogenous HDACs, CKD-581, was studied in vitro and in vivo to determine its effects on the development, invasion, migration, and proliferation of LIHC cell lines. Results: Six HDACs were identified as correlating with the prognosis of LIHC.

Overall survival (OS) was found to be shorter in individuals with higher risk scores when compared to those with lower risk scores, according to survival study. Natural killer cell infiltration was higher in individuals with lower risk ratings, which was mainly explained by the type II interferon (IFN) response. Limiting the activity of endogenous HDACs caused LIHC cell death by preventing their migration, invasion, and proliferation. In vivo studies confirmed that blocking HDAC expression inhibited tumor growth in mice.

Further mechanistic studies showed that inhibition of HDACs expression elevates the protein levels of P21 and P27, and reduces those of cyclins A2, B1, D1 and E1. Conclusions: The risk score prognostic model based on HDAC genes could provide a valuable prognostic biomarker for LIHC. CKD-581 prohibits LIHC progression via inhibiting the cell cycle signaling pathway. CKD-581 holds promise as a therapeutic agent for the clinical management of LIHC.