Objective To investigate the abnormal expression and clinical significance of ACAA1 in hepatocellular carcinoma (HCC).

Methods The transcriptional and protein expression levels of HCC tissues and normal liver tissues were analyzed by the TCGA database, and the expression levels of ACAA1 and their correlation with clinical characteristics were compared. The diagnostic potential of ACAA1 for HCC was evaluated using the receiver operating characteristic (ROC) curves. The effects of ACAA1 on HCC were analyzed through cell proliferation and migration assays.

Results Compared with the normal controls, both mRNA and protein expression levels of ACAA1 were significantly decreased. Their expression levels were negatively correlated with the age of the patients (P < 0.05) and significantly reduced in the cirrhotic patients compared with the non-cirrhotic HCC patients (P < 0.01). The area under the curve (AUC) for ACAA1 mRNA was 0.936 (P < 0.001), with a sensitivity of 90% and specificity of 86.5%. Overexpression of ACAA1 inhibited the proliferation and migration of HCC cells (P < 0.001). Furthermore, ACAA1 expression was negatively correlated with the infiltration of various immune cells, and overexpression of ACAA1 significantly increased the transcriptional level of CD276 in HCC cells (P < 0.001).

Conclusion ACAA1 acts as a tumor suppressor gene in HCC and may serve as a diagnostic and prognostic biomarker for HCC, as well as participate in the regulation of the tumor immune microenvironment.