Published in:
09-10-2021 | Pityriasis Lichenoides Chronica | Original Article
Clinical Significance of Acylphosphatase 1 Expression in Combined HCC-iCCA, HCC, and iCCA
Authors:
Yoshihiro Sakano, Takehiro Noda, Shogo Kobayashi, Akihiro Kitagawa, Yoshifumi Iwagami, Daisaku Yamada, Yoshito Tomimaru, Hirofumi Akita, Kunihito Gotoh, Tadafumi Asaoka, Masahiro Tanemura, Koji Umeshita, Koshi Mimori, Yuichiro Doki, Hidetoshi Eguchi
Published in:
Digestive Diseases and Sciences
|
Issue 8/2022
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Abstract
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.