Department of Obstetrics and Gynecology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Department of Pathology, First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
Diagn Pathol. 2024 Jan 4;19(1):7. doi: 10.1186/s13000-023-01435-4.
Acetyl-CoA acetyltransferase 2 (ACAT2) is a lipid metabolism enzyme and rarely was researched in epithelial ovarian cancer (EOC).
ACAT2 expressions were confirmed in two pairs of cell lines (A2780 and A2780/DDP, OVCAR8 and OVCAR8/DDP) from Gene Expression Omnibus database by bioinformatics analysis, and in A2780 and A2780/DDP cell lines by quantitative real-time polymerase chain reaction and western blotting. Tissue samples were stained by immunohistochemistry and scored for ACAT2 expression. The relationships between ACAT2 expression and clinicopathological characteristics were analyzed by χ test. The prognosis of ACAT2 was analyzed by the log-rank tests and Cox regression models.
ACAT2 was remarkably upregulated in the above drug-resistant cell lines by mRNA (all P < 0.05) and protein expression (P = 0.026) than those in sensitive ones. Patients were classified as ACAT2-high (n = 51) and ACAT2-low (n = 26) according to immunohistochemical score. ACAT2 expression had a significantly inverse correlation with FIGO stage (P = 0.030) and chemo-response (P = 0.041). A marginal statistical significance existed in ACAT2 expression and ascites volume (P = 0.092). Univariate analysis suggested that high-expressed ACAT2 was associated with decreased platinum-free interval (PFI) (8.57 vs. 14.13 months, P = 0.044), progression-free survival (PFS) (14.12 vs. 19.79 months, P = 0.039) and overall survival (OS) (36.89 vs. 52.40 months, P = 0.044). Multivariate analysis demonstrated that ACAT2 expression (hazard ratio = 2.18, 95% confidence interval: 1.15-4.11, P = 0.017) affected OS independently, rather than PFI and PFS.
The expression of ACAT2 in A2780/DDP and OVCAR8/DDP was higher than the corresponding A2780 and OVCAR8. High-expressed ACAT2 was associated with advanced FIGO stage, chemo-resistance, and decreased PFI, PFS and OS. It was an independent prognostic factor of OS in EOC.
乙酰辅酶 A 乙酰基转移酶 2（ACAT2）是一种脂质代谢酶，在卵巢上皮性癌（EOC）中很少被研究。
通过生物信息学分析在基因表达综合数据库中的两对细胞系（A2780 和 A2780/DDP、OVCAR8 和 OVCAR8/DDP）中证实 ACAT2 的表达，并在 A2780 和 A2780/DDP 细胞系中通过实时定量聚合酶链反应和蛋白质印迹法进行检测。免疫组织化学染色对组织样本进行染色并对 ACAT2 表达进行评分。通过卡方检验分析 ACAT2 表达与临床病理特征之间的关系。通过对数秩检验和 Cox 回归模型分析 ACAT2 的预后。
耐药细胞系中 ACAT2 的 mRNA（均 P<0.05）和蛋白表达（P=0.026）均明显高于敏感细胞系。根据免疫组织化学评分，患者分为 ACAT2 高（n=51）和 ACAT2 低（n=26）。ACAT2 表达与 FIGO 分期（P=0.030）和化疗反应（P=0.041）呈显著负相关。ACAT2 表达与腹水体积（P=0.092）存在边缘统计学意义。单因素分析表明，高表达的 ACAT2 与无铂间隔时间（PFI）缩短（8.57 与 14.13 个月，P=0.044）、无进展生存期（PFS）缩短（14.12 与 19.79 个月，P=0.039）和总生存期（OS）缩短（36.89 与 52.40 个月，P=0.044）有关。多因素分析表明，ACAT2 表达（风险比=2.18，95%置信区间：1.15-4.11，P=0.017）是 OS 的独立影响因素，而非 PFI 和 PFS。
A2780/DDP 和 OVCAR8/DDP 中 ACAT2 的表达高于相应的 A2780 和 OVCAR8。高表达的 ACAT2 与 FIGO 分期较晚、化疗耐药以及 PFI、PFS 和 OS 降低有关。它是 EOC 中 OS 的独立预后因素。
