Miyashita Shotaro, Shimizu Takayuki, Niki Maiko, Sato Shun, Tanaka Genki, Yamaguchi Takamune, Park Kwang Hwa, Matsumoto Takatsugu, Shiraki Takayuki, Mori Shozo, Aoki Taku
Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan.
Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
Anticancer Res. 2025 Feb;45(2):651-659. doi: 10.21873/anticanres.17452.
BACKGROUND/AIM: The incidence of hepatocellular carcinoma (HCC) associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatitis C virus sustained virologic response (HCV-SVR) are increasing. However, the mechanisms driving HCC development in these patients remain unclear. This study aimed to evaluate the role of cellular senescence and RNA editing in HCC by examining cyclin-dependent kinase inhibitor 2A (p16) and adenosine deaminase acting on RNA (ADAR1) expression.
HCC specimens from patients with MASLD or HCV-SVR were analyzed by immunohistochemistry to assess p16 and ADAR1 expression. Statistical analyses were conducted using the Chi-squared test, Fisher's exact test, and Mann-Whitney U-test. Survival analyses were performed using the Kaplan-Meier method, the log-rank test, and Cox regression analysis.
Among 122 patients, 59 (48.4%) had MASLD and 63 (51.6%) had HCV-SVR. p16 expression was observed in 69 cases (57.0%) in the noncancerous areas and 53 cases (44.5%) in the cancerous areas. ADAR1 expression was positive in 28 cases (23.5%) in the cancerous areas and significantly associated with p16 expression in the cancerous areas (p=0.039). Patients with p16 expression in the noncancerous areas were older (p=0.045) and had elevated serum ALT levels (p=0.024). p16 expression in the cancerous areas were correlated with a shorter recurrence-free survival (HR=1.65, 95%CI=1.00-2.73, p=0.046).
Cellular senescence and RNA editing may play a key role in MASLD- and HCV-SVR-related HCC. p16 expression in the cancerous areas may serve as a prognostic biomarker for surgical outcomes.
背景/目的：与代谢功能障碍相关脂肪性肝病（MASLD）和丙型肝炎病毒持续病毒学应答（HCV-SVR）相关的肝细胞癌（HCC）发病率正在上升。然而，这些患者中驱动HCC发生发展的机制仍不清楚。本研究旨在通过检测细胞周期蛋白依赖性激酶抑制剂2A（p16）和作用于RNA的腺苷脱氨酶（ADAR1）的表达，评估细胞衰老和RNA编辑在HCC中的作用。
采用免疫组织化学分析来自MASLD或HCV-SVR患者的HCC标本，以评估p16和ADAR1的表达。使用卡方检验、Fisher精确检验和Mann-Whitney U检验进行统计分析。采用Kaplan-Meier法、对数秩检验和Cox回归分析进行生存分析。
在122例患者中，59例（48.4%）患有MASLD，63例（51.6%）患有HCV-SVR。在非癌区域，69例（57.0%）观察到p16表达，在癌区域，53例（44.5%）观察到p16表达。在癌区域，28例（23.5%）ADAR1表达呈阳性，且与癌区域p16表达显著相关（p=0.039）。非癌区域有p16表达的患者年龄较大（p=0.045），血清ALT水平升高（p=！0.024）。癌区域p16表达与无复发生存期较短相关（HR=1.65，95%CI=1.00-2.73，p=0.046）。
细胞衰老和RNA编辑可能在MASLD和HCV-SVR相关的HCC中起关键作用。癌区域p16表达可作为手术结局的预后生物标志物。
