When investigating the clinical significance of acylphosphatase 1 (ACYP1) expression in hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular and cholangiocarcinoma (cHCC-iCCA), a team of Japanese researchers discovered that ACYP1 expression influences tumor growth and cell viability in both HCC and iCCA and thus has an impact on prognosis. The finding was published in Digestive Diseases and Sciences. 

HCC accounts for approximately 85% of primary liver cancers, while iCCA accounts for about 15%. cHCC-iCCA is a primary liver cancer that has histological features of both HCC and iCCA, and it accounts for approximately 1.0% to 4.7% of liver cancers. Surgical resection remains the only curative treatment for all of these malignancies. 

Recently, cancer researchers have been focused on the role of acetate metabolism in cancer pathophysiology. The researchers wrote, “Acetate can be used by tumor cells as bioenergetic fuel or a nutrition source to support lipid bio-synthesis” and that “ACYP1 has been reported to make acetic acid from acetyl phosphate.”

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In addition, ACYP1 has been associated with metastatic colorectal tumors. Sakano et al thus decided to investigate the clinical significance of ACYP1 in these 3 groups of liver cancers. 

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The researchers performed ACYP1 immunohistochemistry in 39 patients who had curative surgery for cHCC-iCCA between January 1999 and December 2017 at the Department of Gastroenterological Surgery at Osaka University Hospital in Japan. They then evaluated prognosis in the 3 groups of liver cancers, which were classified according to the 2018 International Consensus Group. 

The research team wrote, “The relationships between ACYP1 expression and cell viability, migration, invasiveness, and apoptosis were examined using [small interfering RNA] methods in vitro.” Lastly, they investigated the effects of the downregulation of ACYP1 expression on in vivo subcutaneous tumor volumes and cell apoptosis. 

The results demonstrated that high ACYP1 expression significantly lowered overall survival and was an independent prognostic factor in all 3 types of liver cancers studied. Downregulating ACYP1 had the effect of reducing the proliferative capacity, migration, and invasiveness of both HCC and iCCA cells. In addition, the knockdown of ACYP1 induced apoptosis in vivo and inhibited tumor growth.

The researchers concluded, “Our study showed that ACYP1 is a common prognostic factor in both HCC and iCCA and an ideal treatment target of cHCC-iCCA.” 


Sakano Y, Noda T, Kobayashi S, et al. Clinical significance of acylphosphatase 1 expression in combined HCC-iCCA, HCC, and iCCADig Dis Sci. Published online October 9, 2021. doi:10.1007/s10620-021-07266-x