Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

Abstract Background Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles our understanding complicated interaction between metabolic reprogramming tumor immune microenvironment. Methods We compared metabolomic, transcriptomic characteristics portal vein thrombosis (PVTT) primary to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels mRNA two cohorts from published database GEO 60) TCGA 411) were downloaded explore differentially expressed genes functional enriched gene set. Evaluation infiltration estimated validated data both six deconvolution algorithms a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan–Meier multivariable Cox regression model) performed examine prognostic value ACLY, related checkpoints cohort. LASSO further conducted determine panel predict survival outcomes associated ACLY. Results identified novel signature, ATP citrate lyase, metabolomic approaches. demonstrated that metabolism adaptations fatty acid cholesterol biosynthesis triggered by ACLY oncogenic activation. illustrated crucial function its potential CD276, promising target checkpoint blockade, showed correlation differential expression risk classification. Combination CD276 level ACLY-associated predictive model retrieved stratification patients HCC.ACLY blockade counteract activation immunosuppressive status microenvironment highlighted attractive prospect for translational application. Conclusions investigated indispensable metabolism, HCC. anticipate multifaced may reveal mechanistic research combinational therapy, suggesting combination work as strategy.