Sakano Yoshihiro, Noda Takehiro, Kobayashi Shogo, Kitagawa Akihiro, Iwagami Yoshifumi, Yamada Daisaku, Tomimaru Yoshito, Akita Hirofumi, Gotoh Kunihito, Asaoka Tadafumi, Tanemura Masahiro, Umeshita Koji, Mimori Koshi, Doki Yuichiro, Eguchi Hidetoshi
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka, 565-0871, Japan.
Department of Surgery, Osaka Police Hospital, Osaka, Japan.
Dig Dis Sci. 2022 Aug;67(8):3817-3830. doi: 10.1007/s10620-021-07266-x. Epub 2021 Oct 9.
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.
We evaluated the clinical significance of ACYP1 expression in cHCC-iCCA, HCC, and iCCA.
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.
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.
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.
肝内胆管癌合并肝细胞癌是一种罕见的原发性肝癌，具有肝细胞癌和肝内胆管癌的组织学特征。关于肝内胆管癌合并肝细胞癌的预后特征和分子机制知之甚少。酰基磷酸酶1是一种胞质酶，可从乙酰磷酸产生乙酸，并在癌症进展中起重要作用。
我们评估了ACYP1表达在肝内胆管癌合并肝细胞癌、肝细胞癌和肝内胆管癌中的临床意义。
对39例诊断为肝内胆管癌合并肝细胞癌的病例进行ACYP1免疫组织化学检测。在三个不同队列（肝内胆管癌合并肝细胞癌、肝细胞癌和肝内胆管癌）中评估预后。使用小干扰RNA方法在体外检测ACYP1表达与细胞活力、迁移、侵袭和凋亡之间的关系。在下调ACYP1表达后，评估体内皮下肿瘤体积和细胞凋亡情况。
几乎一半的肝内胆管癌合并肝细胞癌患者被诊断为ACYP1高表达。在所有三个队列中，ACYP1高表达的病例总生存期显著较低，并且高ACYP1表达被确定为独立的预后因素。ACYP1的下调降低了肝细胞癌和肝内胆管癌细胞的增殖能力、迁移和侵袭能力。此外，敲低ACYP1增加了凋亡细胞的比例，并降低了抗凋亡蛋白的表达。ACYP1小干扰RNA转染显著抑制了体内肿瘤生长，并且凋亡细胞数量增加。
ACYP1高表达可能影响肝内胆管癌合并肝细胞癌、肝细胞癌和肝内胆管癌患者的预后。在体外，ACYP1表达通过调节抗凋亡蛋白影响肝细胞癌和肝内胆管癌的肿瘤生长和细胞活力。
