Conclusion
Our study proposes a dual-targeted therapeutic strategy for HCC, which may represent a promising treatment approach.
Methods
This study identified genes linked to HCC progression via differential analysis. Key genes were identified through univariate and multivariate Cox regression analysis. The biological effects of co-expressed CRHBP and CFHR3 were evaluated in vitro. mRNAs encoding CRHBP and CFHR3 were encapsulated in lipid nanoparticles (LNPs), with the addition of SP94 peptide on the LNPs surface to enhance targeting. The therapeutic efficacy of dual-mRNA LNPs was evaluated in HCC cells and mouse models.
Purpose
Hepatocellular carcinoma (HCC) is a deadly disease requiring the identification of new therapeutic targets and strategies.
Results
CRHBP and CFHR3 were closely associated with HCC progression. Low expression of CRHBP (P < 0.01, HR = 1.931 [1.174-3.175]) and CFHR3 (P < 0.05, HR = 1.755 [1.066-2.890]) was identified as a poor prognostic factor for HCC. The risk score model combining CRHBP and CFHR3 demonstrated superior predictive power (P < 0.001, HR = 2.935 [1.768-4.872]). Co-expression of CRHBP and CFHR3 significantly inhibited the malignant biological functions of HCC cells. Treatment with SP94 peptide-modified dual-mRNA LNPs markedly suppressed HCC tumor growth and exhibited excellent biocompatibility and safety.