Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA.

BACKGROUND: Combined hepatocellular and cholangiocarcinoma is a rare primary liver cancer with histological features of both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Little is known about the prognostic features and molecular mechanism of cHCC-iCCA. Acylphosphatase 1 is a cytosolic enzyme that produces acetic acid from acetyl phosphate and plays an important role in cancer progression. AIMS: We evaluated the clinical significance of ACYP1 expression in cHCC-iCCA, HCC, and iCCA. METHODS: ACYP1 immunohistochemistry was performed in 39 cases diagnosed with cHCC-iCCA. The prognosis was evaluated in three different cohorts (cHCC-iCCA, HCC, and iCCA). The relationships between ACYP1 expression and cell viability, migration, invasiveness, and apoptosis were examined using siRNA methods in vitro. In vivo subcutaneous tumor volumes and cell apoptosis were evaluated after downregulation of ACYP1 expression. RESULTS: Almost half of the patients with cHCC-iCCA were diagnosed with high ACYP1 expression. In all three cohorts, the cases with high ACYP1 expression had significantly lower overall survival, and high ACYP1 expression was identified as an independent prognostic factor. Downregulation of ACYP1 reduced the proliferative capacity, migration, and invasiveness of both HCC and iCCA cells. Moreover, knockdown of ACYP1 increased the ratio of apoptotic cells and decreased the expression of anti-apoptosis proteins. In vivo tumor growth was significantly inhibited by the transfection of ACYP1 siRNA, and the number of apoptotic cells increased. CONCLUSION: High ACYP1 expression could influence the prognosis of cHCC-iCCA, HCC, and iCCA patients. In vitro ACYP1 expression influences the tumor growth and cell viability in both HCC and iCCA by regulating anti-apoptosis proteins.

Effect of ACYP1 on hepatocellular carcinoma immune infiltration and prognosis / 中华肝胆外科杂志

Objective:To investigate the expression, prognostic value of acylphosphatase 1 (ACYP1) and its relationship with hepatocellular carcinoma (HCC) immune cell infiltration.Methods:The expression of ACYP1 in 374 cases of HCC was analyzed by using The Cancer Genome Atlas (TCGA) database. According to the median expression level of ACYP1 in HCC, the patients were divided into high expression (187 cases) and low expression group (187 cases). Fifty normal liver tissue were used as negative control. The differential expression, Kaplan-Meier survival analysis, univariate and multivariate Cox analysis were performed to evaluate the role of ACYP1 in the diagnosis and prognosis of HCC. The relationship between the expression level of ACYP1 and immune cell infiltration and immune checkpoint were analyzed through the TIMER database.Results:The expression level of ACYP1 in HCC (2.18±0.69) was higher than that in normal liver tissue (1.02±0.31), and the difference was statistically significant ( t=11.76, P<0.001). The survival of HCC patients with high ACYP1 was shorter than those HCC patients with low ACYP1 expression, and high expression of ACYP1 was an independent risk factor for poor prognosis of HCC patients ( HR=2.402, 95% CI: 1.483-3.891, P<0.05). The area under the curve of ACYP1 expression level in diagnosis of HCC was 0.965. The expression level of ACYP1 was significantly positively correlated with immune cell infiltration and immune checkpoints programmed cell death protein 1( r=0.288, P<0.001) and cytotoxic T lymphocyte-associated antigen 4 ( r=0.311, P<0.001). Conclusion:ACYP1 is a potential biomarker for HCC diagnosis and prognosis , as well as a potential therapeutic target.