Differential expression and prognostic role of ACACA, ACLY, and FASN in schistosomiasis-associated versus hepatitis B virus-related liver cancer.

OBJECTIVE: To investigate the clinicopathological differences between schistosomiasis-related liver cancer (Sj-LC) and hepatitis B virus-related liver cancer (HBV-LC), as well as the expression and prognostic significance of key lipid metabolism enzymes (ACACA, ACLY, FASN). METHODS: A retrospective analysis was performed on 309 HBV-LC and 44 Sj-LC patients treated at the First Affiliated Hospital of Wannan Medical College from June 2016 to December 2024. AJCC staging was conducted for 183 HBV-LC and 25 Sj-LC cases (June 2016–June 2021). Transcriptome data of 111 HBV-LC cases were retrieved from the Cancer Genome Atlas (TCGA) database for analysis. Gender- and age-stratified tissue samples (Sj-LC, HBV-LC, and normal liver tissues) were subjected to immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (RT-qPCR) to detect the expression of ACACA, ACLY, and FASN. RESULTS: Compared with HBV-LC, Sj-LC had a lower male proportion (68.2% vs. 86.1%, P = 0.003), an older age at onset (66.38 ± 8.364 vs. 60.75 ± 11.682 years, P < 0.001), a lower proportion of hepatocellular carcinoma (P < 0.001), higher incidences of gastrointestinal bleeding, hepatic encephalopathy, metastasis, and extrahepatic spread (all P < 0.05), and a more advanced tumor stage (predominantly IVB, P < 0.001). Sj-LC also exhibited higher levels of D-dimer, cholesterol, and triglycerides (all P < 0.01). Bioinformatics analysis showed upregulated expression of ACACA, ACLY, and FASN in HBV-LC. IHC and RT-qPCR results confirmed higher expression of these enzymes in Sj-LC (larger positive areas, stronger staining intensity, and higher amplification folds), with ACLY expression significantly overexpressed compared to normal liver tissues. CONCLUSION: Sj-LC exhibits distinct clinicopathological features and lipid metabolism enzyme expression profiles compared with HBV-LC, characterized by older onset age, more complications, stronger invasiveness, and advanced stage at diagnosis. Elevated ACACA, ACLY, and FASN expression suggests that lipid metabolism reprogramming may be associated with the malignant phenotype of Sj-LC. Notably, these enzymes were not confirmed as independent prognostic factors for Sj-LC, and their direct association with prognosis requires further verification in expanded cohorts. Targeted individualized diagnosis, treatment, and early screening strategies are warranted for Sj-LC.